http://www.bibsonomy.org/burst/user/biblio24/mappingBibSonomy BuRST Feed for /user/biblio24/mapping2008-07-21T00:45:56+02:00http://www.bibsonomy.org/bibtex/264fee8a74054cacb021a4106ed8baf1f/biblio24biblio242006-07-07T01:10:50+02:00mapping spr apob epitope <span style="color:#555555;">L. <a href="http://www.bibsonomy.org/author/Laricchia Robbio">Laricchia Robbio</a> and P. <a href="http://www.bibsonomy.org/author/Uboldi">Uboldi</a> and S. <a href="http://www.bibsonomy.org/author/Marcovina">Marcovina</a> and R. P. <a href="http://www.bibsonomy.org/author/Revoltella">Revoltella</a> and A. L. <a href="http://www.bibsonomy.org/author/Catapano">Catapano</a> </span><em>Biosens Bioelectron</em><em>16(9-12):963--969</em><em>December2001. </em>Fri Jul 07 01:10:50 CEST 2006Institute of Mutagenesis and Differentiation, CNR, Area della Ricerca San Cataldo, 56100 Via Moruzzi, Ghezzano-Pisa, Italy. lel@imd.pi.cnr.itBiosens BioelectronDecember9-12963--969Epitope mapping analysis of apolipoprotein B-100 using a surface plasmon resonance-based biosensor.162001mapping spr apob epitope Using a surface plasmon resonance (SPR)-based biosensor (BIA-technology), we have studied the interaction of ten different murine monoclonal antibodies (mAbs, all IgG(1)), raised against the main protein constituent of human low density lipoprotein (LDL), i.e. the apolipoprotein B-100 (apoB-100). These mAbs identify distinct domains on apoB-100, relevant to LDL-receptor interaction: epitopes in the amino-terminal region (mAbs L7, L9, L10 and L11: aa 1-1297) and in the middle region (mAb 6B: aa 1480-1693; mAbs 2A, 3B: aa 2152-2377; mAbs 9A, L2 and L4: aa 2657-3248) of native apoB-100. A multisite binding analysis was performed to further characterize the epitopes recognized by all these mAbs. A rabbit anti-mouse IgG(1)-Fc antibody (RAM.Fc) was first coupled to the gold surface in order to capture one anti-human apoB-100 mAb. ApoB-100 protein was subsequently injected and allowed to react with this immobilized, oriented antibody. Multisite binding assays were then performed, by sequentially flowing other mAbs, in different orders, over the sensing surface. The capacity of each mAb to interact with the entrapped apoB-100 in a multimolecular complex was monitored in real time by SPR. The results achieved were comparable to those obtained by western immunoblotting using the same reagents. However, SPR ensures a more detailed epitope identification, demonstrating that BIA-technology can be successfully used for mapping distinct epitopes on apoB-100 protein in solution dispensing with labels and secondary tracers; moreover, compared with conventional immunoassays, it is significantly time saving (CNR-P.F. MADESS 2).http://www.bibsonomy.org/bibtex/28470a55ffd3031830371a1e0072d15bf/biblio24biblio242006-07-07T01:10:50+02:00apob epitope mapping <span style="color:#555555;">S. <a href="http://www.bibsonomy.org/author/Fantappiè">Fantappi&#232;</a> and A. <a href="http://www.bibsonomy.org/author/Corsini">Corsini</a> and A. <a href="http://www.bibsonomy.org/author/Sidoli">Sidoli</a> and P. <a href="http://www.bibsonomy.org/author/Uboldi">Uboldi</a> and A. <a href="http://www.bibsonomy.org/author/Granata">Granata</a> and T. <a href="http://www.bibsonomy.org/author/Zanelli">Zanelli</a> and P. <a href="http://www.bibsonomy.org/author/Rossi">Rossi</a> and S. <a href="http://www.bibsonomy.org/author/Marcovina">Marcovina</a> and R. <a href="http://www.bibsonomy.org/author/Fumagalli">Fumagalli</a> and A. L. <a href="http://www.bibsonomy.org/author/Catapano">Catapano</a> </span><em>Journal of Lipid Research</em><em>33(8):1111--1121</em><em>August1992. </em>Fri Jul 07 01:10:50 CEST 2006Institute of Pharmacological Sciences, University of Milano, Italy.Journal of Lipid ResearchAugust81111--1121Monoclonal antibodies to human low density lipoprotein identify distinct areas on apolipoprotein B-100 relevant to the low density lipoprotein-receptor interaction.331992apob epitope mapping We have characterized the epitopes for ten murine monoclonal antibodies (Mabs) to human low density lipoprotein (LDL) and studied their ability to interfere with the LDL-receptor interaction. The epitopes for the antibodies were defined by using the following approaches: 1) interaction with apoB-48; 2) interaction with apoB-100 thrombolytic fragments; and 3) interaction with beta-galactosidase-apoB fusion proteins spanning different areas of the apoB-100 sequence. The results obtained are consistent with the following map of epitopes: Mab 6E, amino acids (aa) 1-1297, Mabs 5A and 6B, aa 1480-1693, Mabs 2A, 7A, 3B, and 4B, aa 2152-2377, Mabs 8A and 9A, aa 2657-3248 and 3H, aa 4082-4306. Four Mabs (2A, 5A, 7A, and 9A) whose epitopes are located in three different areas of apoB, dramatically reduced (up to 95%) the LDL-receptor interaction on cultured human fibroblasts; Fab fragments were as effective as the whole antibodies. Mab 3H, on the other hand, increased LDL binding up to threefold. These findings are consistent with the hypothesis that several areas of apoB-100 are involved independently or in concert in modulating the apoprotein B conformation required for interaction with the LDL receptor.http://www.bibsonomy.org/bibtex/2168fabbe738c303ba879cabba2132262/biblio24biblio242006-07-07T01:10:50+02:00apob epitope mapping <span style="color:#555555;">A. <a href="http://www.bibsonomy.org/author/Law">Law</a> and J. <a href="http://www.bibsonomy.org/author/Scott">Scott</a> </span><em>Journal of Lipid Research</em><em>31(6):1109--1120</em><em>June1990. </em>Fri Jul 07 01:10:50 CEST 2006Division of Molecular Medicine, Clinical Research Centre, Harrow, Middlesex, UK.Journal of Lipid ResearchJune61109--1120A cross-species comparison of the apolipoprotein B domain that binds to the LDL receptor.311990apob epitope mapping Apolipoprotein (apo)-B-100 is the ligand that mediates the clearance of low density lipoprotein (LDL) from the circulation by the apoB,E (LDL) receptor pathway. Clearance is mediated by the interaction of a domain enriched in basic amino acid residues on apoB-100 with clusters of acidic residues on the apoB,E (LDL) receptor. A model has been proposed for the LDL receptor binding domain of apoB-100 based on the primary amino acid sequence (Knott, T. J., et al. 1986. Nature. 323: 734-738). Two clusters of basic residues (A: 3147-3157 and B: 3359-3367) are apposed on the surface of the LDL particle by a disulfide bridge between Cys 3167 and 3297. Support for this single domain model has been obtained from the mapping of epitopes for anti-apoB monoclonal antibodies that block the binding of apoB to the LDL receptor. Here we test this model by comparing the nucleotide (from 9623 to 10,442) and amino acid sequence (from 3139 to 3411) of apoB-100 in seven species (human, pig, rabbit, rat, Syrian hamster, mouse, and chicken). Overall, this region is highly conserved. Cluster B maintains a strong net positive charge and is homologous across species in both primary and secondary structure. However, the net positive charge of region A is not conserved across these species, but the region remains strongly hydrophilic. The secondary structure of the region between clusters A and B is preserved, but the disulfide bond is unique to the human sequence. This study suggests that the basic region B is primarily involved in the binding of apoB-100 to the apoB,E (LDL) receptor.http://www.bibsonomy.org/bibtex/28d11f0f4ea344a79847956672e32e594/biblio24biblio242006-07-07T01:10:50+02:00mapping apob epitope <span style="color:#555555;">A. <a href="http://www.bibsonomy.org/author/Leroy">Leroy</a> and G. <a href="http://www.bibsonomy.org/author/Castro">Castro</a> and G. <a href="http://www.bibsonomy.org/author/Agnani">Agnani</a> and R. <a href="http://www.bibsonomy.org/author/Saïle">Sa&#239;le</a> and A. <a href="http://www.bibsonomy.org/author/Barkia">Barkia</a> and J. C. <a href="http://www.bibsonomy.org/author/Fruchart">Fruchart</a> </span><em>J Lipid Res</em><em>33(6):889--898</em><em>June1992. </em>Fri Jul 07 01:10:50 CEST 2006SERLIA, Institut Pasteur et INSERM U 279, Lille, France.J Lipid ResJune6889--898Thrombin cleavage of apolipoprotein Bh of rabbit LDL: structural comparisons with human apolipoprotein B-100.331992mapping apob epitope Rabbit plasma low density lipoprotein (LDL) contains one major apolipoprotein of apparent molecular weight of 320 kDa, designated apolipoprotein (apo) Bh, while another component termed apoB1 of apparent molecular weight of 220 kDa is found in chylomicrons. The fragments generated by thrombin digestion of the protein moieties of rabbit and human LDL were separated by polyacrylamide gradient gel electrophoresis and compared. As in the human species, the enzyme produced limited cleavage patterns of rabbit LDL apoB. Within the first 2 h, two fragments (Tr1 and Tr2, with apparent molecular weights 280,000 and 44,000, respectively) appeared. Longer incubations led to the production of two additional peptides, Tr3 and Tr4 (apparent molecular weights 180,000 and 96,000, respectively). Ten monoclonal antibodies, developed against rabbit LDL and designated P01 to P10, were found to react with rabbit apoB. Some also cross-reacted with human apoB. Epitope mapping, performed with these antibodies, showed that Tr3 and Tr4 were derived from the further degradation of Tr1. The rabbit is one of the most frequently used animals in atherosclerosis research. Its LDL receptor has been characterized and there exists a strain of homozygous LDL receptor-deficient rabbits referred to as WHHL rabbits. Despite this, little has been done to characterize the structure of rabbit apoB; only a short region has been sequenced and shown to be the carboxyl-terminal region, the rabbit apoB1. The molecular weight of human apoB (550,000) is much larger than rabbit apoBh. In both species, a primary and secondary thrombin cleavage occur, but the size of the fragments produced is very different between the two species. Identification of the thrombolytic fragments of the rabbit apoB have afforded the opportunity to compare the structures of both apoB species.http://www.bibsonomy.org/bibtex/22ce679c5f6641476344be6928398ae71/biblio24biblio242006-07-07T01:10:50+02:00apob mapping epitope <span style="color:#555555;">R. <a href="http://www.bibsonomy.org/author/Milne">Milne</a> and R. <a href="http://www.bibsonomy.org/author/Théolis">Th&#233;olis</a> and R. <a href="http://www.bibsonomy.org/author/Maurice">Maurice</a> and R. J. <a href="http://www.bibsonomy.org/author/Pease">Pease</a> and P. K. <a href="http://www.bibsonomy.org/author/Weech">Weech</a> and E. <a href="http://www.bibsonomy.org/author/Rassart">Rassart</a> and J. C. <a href="http://www.bibsonomy.org/author/Fruchart">Fruchart</a> and J. <a href="http://www.bibsonomy.org/author/Scott">Scott</a> and Y. L. <a href="http://www.bibsonomy.org/author/Marcel">Marcel</a> </span><em>The Journal of Biological Chemistry</em><em>264(33):19754--19760</em><em>November1989. </em>Fri Jul 07 01:10:50 CEST 2006Laboratory of Lipoprotein Metabolism, Institut de Recherches Cliniques de Montréal, Quebec, Canada.The Journal of Biological ChemistryNovember3319754--19760The use of monoclonal antibodies to localize the low density lipoprotein receptor-binding domain of apolipoprotein B.2641989apob mapping epitope Human apolipoprotein (apo) B-100 is composed of 4536 amino acids. It is thought that the binding of apoB to the low density lipoprotein (LDL) receptor involves an interaction between basic amino acids of the ligand and acidic residues of the receptor. Three alternative models have been proposed to describe this interaction: 1) a single region of apoB is involved in receptor binding; 2) groups of basic amino acids from throughout the apoB primary structure act in concert in apoB receptor binding; and 3) apoB contains multiple independent binding regions. We have found that monoclonal antibodies (Mabs) specific for a region that spans a thrombin cleavage site at apoB residue 3249 (T2/T3 junction) totally blocked LDL binding to the LDL receptor. Mabs specific for epitopes outside this region had either no or partial ability to block LDL binding. In order to define the region of apoB directly involved in the interaction with the LDL receptor we have tested 22 different Mabs for their ability to bind to LDL already fixed to the receptor. A Mab specific for an epitope situated between residues 2835 and 2922 could bind to its epitope on LDL fixed to its receptor whereas a second epitope between residues 2980 and 3084 is inaccessible on receptor-bound LDL. A series of epitopes near residue 3500 of apoB is totally inaccessible, and another situated between residues 4027 and 4081 is poorly accessible on receptor-bound LDL. In contrast, an epitope that is situated between residues 4154 and 4189 is fully exposed. Mabs specific for epitopes upstream and downstream of the region 3000-4000 can bind to receptor-bound LDL with a stoichiometry close to unity. Our results strongly suggest that the unique region of apoB directly involved in the LDL-receptor interaction is that of the T2/T3 junction.http://www.bibsonomy.org/bibtex/23b05a4543a044aec50b7c949a22dab22/biblio24biblio242006-07-07T01:10:50+02:00apob epitope mapping <span style="color:#555555;">P. F. <a href="http://www.bibsonomy.org/author/Chen">Chen</a> and Y. L. <a href="http://www.bibsonomy.org/author/Marcel">Marcel</a> and C. Y. <a href="http://www.bibsonomy.org/author/Yang">Yang</a> and A. M. <a href="http://www.bibsonomy.org/author/Gotto">Gotto</a> and R. W. <a href="http://www.bibsonomy.org/author/Milne">Milne</a> and J. T. <a href="http://www.bibsonomy.org/author/Sparrow">Sparrow</a> and L. <a href="http://www.bibsonomy.org/author/Chan">Chan</a> </span><em>European Journal of Biochemistry</em><em>175(1):111--118</em><em>July1988. </em>Fri Jul 07 01:10:50 CEST 2006Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.European Journal of BiochemistryJuly1111--118Primary sequence mapping of human apolipoprotein B-100 epitopes. Comparisons of trypsin accessibility and immunoreactivity and implication for apoB conformation.1751988apob epitope mapping Differential trypsin-accessibility and monoclonal antibodies (Mabs) to human apolipoprotein (apo) B-100 are both important tools for probing apoB structure and conformation on low-density lipoproteins (LDL). In this study, we have mapped greater than 80% of the C-terminal region (720 residues) of LDL apoB-100 using trypsin digestion. Our results extend our previous data [Yang et al. (1986) Nature (Lond.) 323, 738-742] confirming that the C-terminal region of about 420 residues of apoB-100 is largely inaccessible to trypsin, whereas the part just preceding this region has interspersed trypsin-accessible and inaccessible peptides. We have determined the amino acid sequence of specific apoB-100 peptides containing epitopes recognized by four separate Mabs: two epitopes have been mapped to within 20 residues, one has been mapped to 36 residues, and the last to 80 residues. We used polyclonal antisera to identify 16 overlapping clones of varying lengths of apoB-100 cDNAs extending from the C-terminus of apoB-100 cloned in the expression vector, lambda gt11. These clones were then tested against individual Mabs. By nucleotide sequence analysis of overlapping clones that show differential reactivities to different Mabs, we have mapped the individual epitopes of each Mab to within about 50-150 amino acid residues predicted from the DNA sequences. Confirmation and further fine mapping were accomplished by competition for LDL binding using partially purified fusion proteins and chemically synthesized oligopeptides. Two epitopes (Mabs 7 and 22) were mapped to the C-terminal 20 amino acids of apoB-100, one (Mab 16) to residues 4154-4189, and another (Mab 20) to residues 3926-4005. Mab 16 precipitates more than 80% of LDL particles. Mab 20 precipitates only denatured apoB but not native LDL apoB [Milne et al. (1987) Mol. Immunol. 24, 435]. Mabs 7 and 22 are unique in that they precipitate LDL apoB modified by storage much better than freshly isolated LDL-apoB. Although epitope expression and trypsin-accessibility represent two useful probes for the study of protein conformation, there was no obvious correlation between these two parameters when applied to LDL apoB for the antibodies we have examined.http://www.bibsonomy.org/bibtex/2c2f02dd34a1c927e4d1496d639f195f1/biblio24biblio242006-07-07T01:10:50+02:00apob epitope mapping <span style="color:#555555;">A. <a href="http://www.bibsonomy.org/author/Gries">Gries</a> and C. <a href="http://www.bibsonomy.org/author/Fievet">Fievet</a> and S. <a href="http://www.bibsonomy.org/author/Marcovina">Marcovina</a> and J. <a href="http://www.bibsonomy.org/author/Nimpf">Nimpf</a> and H. <a href="http://www.bibsonomy.org/author/Wurm">Wurm</a> and H. <a href="http://www.bibsonomy.org/author/Mezdour">Mezdour</a> and J. C. <a href="http://www.bibsonomy.org/author/Fruchart">Fruchart</a> and G. M. <a href="http://www.bibsonomy.org/author/Kostner">Kostner</a> </span><em>J Lipid Res</em><em>29(1):1--8</em><em>January1988. </em>Fri Jul 07 01:10:50 CEST 2006Institute of Physiology, University of Graz, Austria.J Lipid ResJanuary11--8Interaction of LDL, Lp[a], and reduced Lp[a] with monoclonal antibodies against apoB.291988apob epitope mapping Five monoclonal antibodies (2A, 9A, 6B, L3, L7) produced in mice against human apolipoprotein B were investigated by competitive and inhibitive electroimmunoassay (EIA) for their reactivity with low density lipoprotein (LDL), lipoprotein[a] (Lp[a]), and reduced Lp[a]. All of the antibodies reacted with apoB of the different lipoproteins indicated by very similar slopes of the binding curves. None of them gave a positive reaction with apolipoprotein[a]. The amount of apoB required for 50% inhibition of antibody binding varied for the different antibodies and lipoproteins. Antibody 9A showed almost the same affinity for LDL, Lp[a], and reduced Lp[a]. Antibodies 2A and 6B bound about twofold better to LDL and reduced Lp[a] than to untreated Lp[a]. Antibodies L3 and L7 needed nearly threefold higher amounts of Lp[a]-apoB for 50% inhibition of antibody binding than of apoB of LDL and reduced Lp[a]. The amount of apoB required for 50% inhibition of antibody binding was somewhat higher in inhibitive assay than in competitive assay. We suggest that apo[a] covers certain epitopes of apoB in native Lp[a] leading to a reduced reaction with the monoclonal antibodies. However, it could also be that the binding of the [a]antigen to apoB via disulfide bridges causes profound conformational changes of the apoB region exposed to the surface.http://www.bibsonomy.org/bibtex/277181e1e36e463d480884749cef04545/biblio24biblio242006-07-07T01:10:50+02:00apob epitope mapping <span style="color:#555555;">X. <a href="http://www.bibsonomy.org/author/Wang">Wang</a> and R. <a href="http://www.bibsonomy.org/author/Bucala">Bucala</a> and R. <a href="http://www.bibsonomy.org/author/Milne">Milne</a> </span><em>Proc Natl Acad Sci U S A</em><em>95(13):7643--7647</em><em>June1998. </em>Fri Jul 07 01:10:50 CEST 2006Lipoprotein and Atherosclerosis Group, University of Ottawa Heart Institute, Ottawa, ON, Canada K1Y 4E9.Proc Natl Acad Sci U S AJune137643--7647Epitopes close to the apolipoprotein B low density lipoprotein receptor-binding site are modified by advanced glycation end products.951998apob epitope mapping Advanced glycation end products (AGEs) are thought to contribute to the abnormal lipoprotein profiles and increased risk of cardiovascular disease of patients with diabetes and renal failure, in part by preventing apolipoprotein B (apoB)-mediated cellular uptake of low density lipoproteins (LDL) by LDL receptors (LDLr). It has been proposed that AGE modification at one site in apoB, almost 1,800 residues from the putative apoB LDLr-binding domain, may be sufficient to induce an apoB conformational change that prevents binding to the LDLr. To further explore this hypothesis, we used 29 anti-human apoB mAbs to identify other potential sites on apoB that may be modified by in vitro advanced glycation of LDL. Glycation of LDL caused a time-dependent decrease in its ability to bind to the LDLr and in the immunoreactivity of six distinct apoB epitopes, including two that flank the apoB LDLr-binding domain. ApoB appears to be modified at multiple sites by these criteria, as the loss of glycation-sensitive epitopes was detected on both native glycated LDL and denatured, delipidated glycated apoB. Moreover, residues directly within the putative apoB LDLr-binding site are not apparently modified in glycated LDL. We propose that the inability of LDL modified by AGEs to bind to the LDLr is caused by modification of residues adjacent to the putative LDLr-binding site that were undetected by previous immunochemical studies. AGE modification either eliminates the direct participation of the residues in LDLr binding or indirectly alters the conformation of the apoB LDLr-binding site.http://www.bibsonomy.org/bibtex/20c871b9efb66a25cb92ee7b93cfa8622/biblio24biblio242006-07-07T01:10:50+02:00epitope apob mapping <span style="color:#555555;">S. G. <a href="http://www.bibsonomy.org/author/Young">Young</a> and R. K. <a href="http://www.bibsonomy.org/author/Koduri">Koduri</a> and R. K. <a href="http://www.bibsonomy.org/author/Austin">Austin</a> and D. J. <a href="http://www.bibsonomy.org/author/Bonnet">Bonnet</a> and R. S. <a href="http://www.bibsonomy.org/author/Smith">Smith</a> and L. K. <a href="http://www.bibsonomy.org/author/Curtiss">Curtiss</a> </span><em>Journal of Lipid Research</em><em>35(3):399--407</em><em>March1994. </em>Fri Jul 07 01:10:50 CEST 2006Gladstone Institute for Cardiovascular Disease, Department of Medicine, University of California, San Francisco 94141-9100.Journal of Lipid ResearchMarch3399--407Definition of a nonlinear conformational epitope for the apolipoprotein B-100-specific monoclonal antibody, MB47.351994epitope apob mapping The apolipoprotein (apo) B-100-specific monoclonal antibody MB47 has been widely used in lipoprotein metabolism and atherosclerosis research. When bound to apoB-100 on low density lipoproteins (LDL), antibody MB47 completely blocks the binding of LDL to the LDL receptor. The epitope for antibody MB47 has previously been mapped to the vicinity of apoB-100 amino acid (aa) residue 3500. To map the epitope for antibody MB47 more precisely, we used recombinant bacterial fusion proteins. Antibody MB47 bound strongly to a fusion protein containing apoB-100 aa 3214-3728, but no specific binding was observed to fusion proteins containing aa 3214-3351, 3214-3506, 3351-3506, or a fusion protein containing aa 3214-3351 and 3506-3728. Although antibody MB47 did not bind to aa 3214-3506, it did bind to aa 3214-3510. Further fusion protein studies revealed that antibody MB47 bound to aa 3429-3510, but bound only very weakly to aa 3453-3510, indicating that aa 3429-3453 constitute an important part of the MB47 epitope. Subsequent fusion protein studies revealed that MB47 bound much more strongly to aa 3429-3523, 3429-3544, 3429-3565, and 3429-3590 than to aa 3429-3510. Thus, aa 3507-3523 also constitute an important part of the MB47 epit0pe. m In summary, the fusion protein data indicated that two nonlinear domains of apoB-100 separated by - 53 aa (the 25 residues from aa 3429 to 3453 and the 17 residues from aa 3507 to 3523) form key parts of the MB47 epitope. Antibody MB47 failed to bind to any of 15 different synthetic apoB peptides that spanned aa 3415-3510, a finding that is consistent with the fusion protein data indicating that the MB47 epitope is formed by the conformational alignment of discontinuous amino acid sequences.http://www.bibsonomy.org/bibtex/2e14ee9c0edf81e44b4597a63373ee56f/biblio24biblio242006-07-07T01:10:50+02:00epitope apob mapping <span style="color:#555555;">L. <a href="http://www.bibsonomy.org/author/Viens">Viens</a> and L. <a href="http://www.bibsonomy.org/author/Lagrost">Lagrost</a> </span><em>J Lipid Res</em><em>38(6):1129--1138</em><em>June1997. </em>Fri Jul 07 01:10:50 CEST 2006Laboratoire de Biochimie de Lipoprotéines, INSERM CJF 93-10, Faculté de Médecine, Dijon, France.J Lipid ResJune61129--1138Effect of lipid transfer activity and triglyceride hydrolysis on apolipoprotein B immunoreactivity in modified low density lipoproteins.381997epitope apob mapping Consequences of alterations in the size and the lipid composition of low density lipoproteins (LDL) on apolipoprotein (apo) B immunoreactivity were analyzed using two distinct anti-apoB monoclonal antibodies (Mabs), i.e., 4G3, which recognizes an epitope closed to the binding site to the LDL receptor, and 2D8, which is directed against a distal region. Inhibition analysis revealed that the lipid transfer-mediated triglyceride enrichment of LDL isolated from 12 native human plasmas is associated with significant reductions in the expression of 2D8 and 4G3 epitopes (P < 0.05 in both cases). In contrast, triglyceride hydrolysis of triglyceride-rich LDL significantly increased apoB immunoreactivity as compared with non-lipolyzed counterparts (P < 0.05 with 2D8 and 4G3 Mabs). Among all the modified LDL fractions studied (n = 36), immunoreactivity of 2D8 and 4G3 epitopes correlated negatively and significantly with the triglyceride content (P < 0.01 in both cases), but with neither the size nor the other lipid parameters of LDL particles. Furthermore, changes in the triglyceride content of LDL correlated significantly with changes in apoB immunoreactivity after in vitro treatment with either lipid transfer activity alone (P < 0.01 with 2D8 and 4G3 Mabs) or lipid transfer activity combined with triglyceride hydrolysis (P < 0.01 with 2D8 and 4G3 Mabs). Finally, both the triglyceride content of native LDL and the total triglyceride level in 12 normolipidemic human plasmas correlated negatively and significantly with the expression of 2D8 epitope (P < 0.03 in both cases) and 4G3 epitope (P < 0.02 in both cases). It is concluded that triglycerides constitute a major determinant of the immunoreactivity of 2D8 and 4G3 apoB epitopes in LDL.http://www.bibsonomy.org/bibtex/2acca9a5e11f5de28586667a664f1e859/biblio24biblio242006-07-07T01:10:50+02:00epitope apob mapping <span style="color:#555555;">S. <a href="http://www.bibsonomy.org/author/Negri">Negri</a> and P. <a href="http://www.bibsonomy.org/author/Roma">Roma</a> and R. <a href="http://www.bibsonomy.org/author/Fogliatto">Fogliatto</a> and P. <a href="http://www.bibsonomy.org/author/Uboldi">Uboldi</a> and S. <a href="http://www.bibsonomy.org/author/Marcovina">Marcovina</a> and A. L. <a href="http://www.bibsonomy.org/author/Catapano">Catapano</a> </span><em>Atherosclerosis</em><em>101(1):37--41</em><em>June1993. </em>Fri Jul 07 01:10:50 CEST 2006Institute of Pharmacological Sciences, University of Milano, Italy.AtherosclerosisJune137--41Immunoreactivity of apo B towards monoclonal antibodies that inhibit the LDL-receptor interaction: effects of LDL oxidation.1011993epitope apob mapping We studied the immunochemical stability of the epitopes for six monoclonal antibodies to human apolipoprotein B-100 upon Cu(2+)-mediated (20 microM) oxidation of LDL. The antibodies used in this study, some of which are known to interfere with the interaction of LDL with their cellular receptors, recognize epitopes in the amino terminal region (Mb 19), in the middle part (6B, 2A, 7A, and 9A) and near aa 3500 (Mb 47) of native apo B. All antibodies except one (7A) recognized native and oxidized LDL (OxLDL) equally well; the immunoreactivity of the epitope for Ab 7A was markedly reduced upon LDL oxidation. Since antibodies 2A, 7A, 9A, and Mb 47 inhibit the LDL-receptor interaction and OxLDL poorly interact in vitro with the LDL receptor we conclude that: (1) various epitopes for monoclonal antibodies against native apo B are spared upon LDL oxidation; and (2) the epitopes for antibodies 2A, 9A, and Mb 47 do not define a unique domain of apo B directly involved in the binding of LDL to their receptor.http://www.bibsonomy.org/bibtex/2707c5aebeba697dc4c64731bf2795c4c/biblio24biblio242006-07-07T01:10:50+02:00spr mapping methodology epitope <span style="color:#555555;">B. <a href="http://www.bibsonomy.org/author/Johne">Johne</a> and M. <a href="http://www.bibsonomy.org/author/Gadnell">Gadnell</a> and K. <a href="http://www.bibsonomy.org/author/Hansen">Hansen</a> </span><em>J Immunol Methods</em><em>160(2):191--198</em><em>April1993. </em>Fri Jul 07 01:10:50 CEST 2006Diagnostica R \& D, Nycomed Pharma AS, Oslo, Norway.J Immunol MethodsApril2191--198Epitope mapping and binding kinetics of monoclonal antibodies studied by real time biospecific interaction analysis using surface plasmon resonance.1601993spr mapping methodology epitope The interaction between human heart myoglobin and ten specific monoclonal antibodies was investigated with a new biosensor technology, real time biospecific interaction analysis (RT BIA), using surface plasmon resonance. Analysis of association and dissociation kinetics was monitored in real time, with unlabelled reactants. Antibody isotyping was rapid and simple. Epitope mapping with RT BIA confirmed, with substantial time saving, the sum of results obtained in conventional labelled systems. Monoclonal antibodies with four different epitope specificities and optimal binding function were selected for a myoglobin sandwich assay with enhanced sensitivity. BIAcore can be used directly as a diagnostic tool, or as an analytical tool in immunoassay development.http://www.bibsonomy.org/bibtex/2ede10db90ef6d276b488842c0fa6095f/biblio24biblio242006-07-07T01:10:50+02:00mapping epitope apob <span style="color:#555555;">C. <a href="http://www.bibsonomy.org/author/Fievet">Fievet</a> and C. <a href="http://www.bibsonomy.org/author/Durieux">Durieux</a> and R. <a href="http://www.bibsonomy.org/author/Milne">Milne</a> and T. <a href="http://www.bibsonomy.org/author/Delaunay">Delaunay</a> and G. <a href="http://www.bibsonomy.org/author/Agnani">Agnani</a> and H. <a href="http://www.bibsonomy.org/author/Bazin">Bazin</a> and Y. <a href="http://www.bibsonomy.org/author/Marcel">Marcel</a> and J. C. <a href="http://www.bibsonomy.org/author/Fruchart">Fruchart</a> </span><em>Journal of Lipid Research</em><em>30(7):1015--1024</em><em>July1989. </em>Fri Jul 07 01:10:50 CEST 2006INSERM U 279 et SERLIA, Institut Pasteur, Lille, France.Journal of Lipid ResearchJuly71015--1024Rat monoclonal antibodies to human apolipoprotein B: advantages and applications.301989mapping epitope apob Eight monoclonal antibodies (Mabs) to human serum low density lipoprotein (LDL) were derived from the fusion of spleen cells, from LOU rats immunized with human LDL, and the rat myeloma line IR983F. These Mabs were characterized in terms of isotype, specificity, and affinity. Competitive experiments indicated that the epitopes that were recognized could be grouped into three patterns depending on their apparent affinity for apoB-containing lipoprotein particles such as LDL, very low density lipoproteins (VLDL), or intermediate density lipoproteins (IDL). Six epitopes have been mapped in relation to elements of the sequence of apolipoprotein B-100 (apoB-100) and some have been assigned to the middle part of the median thrombolytic fragment T3, a region not yet well targeted by mouse Mabs. The presence of lipids for the expression of the epitopes was studied and confirmed a lipid dependence for epitopes that are close to the T2/T3 cleavage site. The capacity of binding to the LDL receptor was also tested; among the Mabs we described, one inhibited the uptake and degradation of LDL to HeLa cells receptor. Finally, some antibodies were able to precipitate LDL in gel.http://www.bibsonomy.org/bibtex/2426d09d1aa1b3094042da65c771a8529/biblio24biblio242006-07-07T01:10:50+02:00mapping epitope apob <span style="color:#555555;">E. S. <a href="http://www.bibsonomy.org/author/Krul">Krul</a> and Y. <a href="http://www.bibsonomy.org/author/Kleinman">Kleinman</a> and M. <a href="http://www.bibsonomy.org/author/Kinoshita">Kinoshita</a> and B. <a href="http://www.bibsonomy.org/author/Pfleger">Pfleger</a> and K. <a href="http://www.bibsonomy.org/author/Oida">Oida</a> and A. <a href="http://www.bibsonomy.org/author/Law">Law</a> and J. <a href="http://www.bibsonomy.org/author/Scott">Scott</a> and R. <a href="http://www.bibsonomy.org/author/Pease">Pease</a> and G. <a href="http://www.bibsonomy.org/author/Schonfeld">Schonfeld</a> </span><em>J Lipid Res</em><em>29(7):937--947</em><em>July1988. </em>Fri Jul 07 01:10:50 CEST 2006Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.J Lipid ResJuly7937--947Regional specificities of monoclonal anti-human apolipoprotein B antibodies.291988mapping epitope apob The usefulness of monoclonal antibodies as probes of protein structure is directly related to knowledge of the structures and locations of the epitopes with which they interact. In this report we provide a detailed map of 13 epitopes on apoB-100 defined by our anti-apoB monoclonal antibodies based on current information on the amino acid sequence of apoB-100. To localize antibody specificities to smaller regions along the linear sequence of the apoB-100 molecule we used a) thrombin- and kallikrein-generated fragments of apoB-100; b) beta-galactosidase- apoB fusion proteins; c) heparin; and d) antibody versus antibody competition experiments. Most of the monoclonal antibodies elicited by immunization with LDL were directed towards epitopes within the first 1279 amino terminal (T4/K2 fragments) or last 1292 carboxyl terminal amino acid residues (T2/K4 fragments) of apoB-100. One epitope localized to the mid-portion of apoB-100 was elicited by immunization with VLDL (D7.2). Saturating amounts of heparin bound to LDL did not inhibit the binding of any of the monoclonal antibodies to their respective epitopes on apoB-100, indicating that none of the antibody determinants is situated close to any of the reported heparin binding sites on LDL apoB. We examined the expression of apoB epitopes on VLDL subfractions and LDL isolated from a normolipidemic donor. The apparent affinities with which the antibodies interacted with their respective epitopes on the VLDL subfractions and LDL uniformly increased as follows: LDL greater than VLDL3 greater than VLDL2 greater than VLDL1, suggesting that each of the major regions of apoB-100 is progressively more exposed as normal VLDL particles become smaller in size and epitopes are most exposed in LDL. Previous experiments utilizing hypertriglyceridemic VLDL subfractions yielded similar results, but the rank order of VLDL subfractions and LDL was not the same for all antibodies tested. Thus, differences in apoB epitope expression on VLDL particles of differing sizes is a general phenomenon, but the expression of apoB epitopes in hypertriglyceridemic VLDL appears to be more heterogeneous than is the case for VLDL from normolipidemic donors.(ABSTRACT TRUNCATED AT 400 WORDS)http://www.bibsonomy.org/bibtex/2224a8336e8cd6eb4bc212b54b6964eb1/biblio24biblio242006-07-07T01:10:50+02:00epitope apob mapping <span style="color:#555555;">E. <a href="http://www.bibsonomy.org/author/Gherardi">Gherardi</a> and A. <a href="http://www.bibsonomy.org/author/Hutchings">Hutchings</a> and G. <a href="http://www.bibsonomy.org/author/Galfre">Galfre</a> and D. E. <a href="http://www.bibsonomy.org/author/Bowyer">Bowyer</a> </span><em>Biochem J</em><em>252(1):237--245</em><em>May1988. </em>Fri Jul 07 01:10:50 CEST 2006Department of Pathology, University of Cambridge, U.K.Biochem JMay1237--245Rat monoclonal antibodies to rabbit and human serum low-density lipoprotein.2521988epitope apob mapping A total of 16 hybrid myeloma clones secreting monoclonal antibodies (McAb) to rabbit or human serum low-density lipoprotein (LDL) were derived from the fusion of spleen cells from LOU or DA rats immunized with rabbit or human LDL and the rat myeloma lines Y3 Ag1.2.3 or YB2/0. Anti-(rabbit LDL) McAb showed limited reactivity with LDL from human, rhesus-monkey, rat and mouse serum. Six out of seven anti-(human LDL) McAb reacted with rhesus-monkey LDL, and only one showed partial cross-reaction with rabbit LDL. Binding-competition experiments indicated that the epitopes recognized by the anti-(rabbit LDL) IgG could be grouped into two major clusters: McAb in the first cluster reacted either with apo-(lipoprotein B-100) (apoB-100) and apo-(lipoprotein B-74) (apoB-74) or with apoB-100 but not with apo-(lipoprotein B-48) (apoB-48), the lower-Mr form of apoB of intestinal origin; the McAb in the second cluster all reacted with apoB-48 in addition to apoB-100 or apoB-100 and apoB-74. The six anti-(human LDL) IgG bound to separate epitopes on LDL. Further data on the epitope specificity of these McAb were obtained by antibody blotting after partial proteolysis of apoB-100 with trypsin or staphylococcal V8 proteinase, and the data confirmed the results obtained with the binding-competition experiments. One McAb to rabbit LDL inhibited the binding of LDL to the fibroblast LDL receptor (50% inhibition at a McAb/LDL molar ratio of 10). A similar result was produced by two other McAb at higher concentrations of antibody.http://www.bibsonomy.org/bibtex/2ee9ede7a23e0296357d8cf117f5d7b20/biblio24biblio242006-07-07T01:10:50+02:00mapping apob epitope <span style="color:#555555;">A. A. <a href="http://www.bibsonomy.org/author/Korotaeva">Korotaeva</a> and N. K. <a href="http://www.bibsonomy.org/author/Golovanova">Golovanova</a> and T. N. <a href="http://www.bibsonomy.org/author/Vlasik">Vlasik</a> and E. V. <a href="http://www.bibsonomy.org/author/Yanushevskaya">Yanushevskaya</a> and V. P. <a href="http://www.bibsonomy.org/author/Tsibulsky">Tsibulsky</a> and V. V. <a href="http://www.bibsonomy.org/author/Yakushkin">Yakushkin</a> and M. G. <a href="http://www.bibsonomy.org/author/Tvorogova">Tvorogova</a> and A. D. <a href="http://www.bibsonomy.org/author/Morozkin">Morozkin</a> and N. V. <a href="http://www.bibsonomy.org/author/Prokazova">Prokazova</a> </span><em>Biochemistry (Mosc)</em><em>63(12):1430--1437</em><em>December1998. </em>Fri Jul 07 01:10:50 CEST 2006Institute of Experimental Cardiology, Cardiology Research Center, Russian Academy of Medical Sciences, Moscow, 121552, Russia. korot@cardio.med.msu.su.Biochemistry (Mosc)December121430--1437Immunoreactivity of apolipoprotein B-100 and binding to LDL-receptor of phospholipase A2-treated low density lipoproteins.631998mapping apob epitope Lipid--protein particles were obtained by treatment of low density lipoproteins (LDL) with phospholipase A2 from bee venom. Under these conditions, half of the phosphatidylcholine (PC) of LDL was changed to lysophosphatidylcholine (LPC). At the same time, the composition of other lipids and the apoprotein structure were unaffected. Three monoclonal antibodies (MAbs) against various apo B epitopes were used to test immunoreactivity of phospholipase A2-treated LDL (pl-LDL). The apo B epitope interacting with MAb 4C11 (amino acid residues 2377-2658) showed significantly decreased immunoreactivity. Increase in MAb 4C11 binding was demonstrated to depend on oxidation degree of LDL. Thus, changing of half of PC to LPC modified apo B translocation in the lipoprotein globule in an opposite manner as compared with changes induced by oxidative modification. A minor increase in immunoreactivity of pl-LDL with 1D1 MAb against a large middle part of apo B (residues 1297-3249) may be due to the effect of the change of surface lipid composition on the extent of immersion of apo B into the hydrophobic phase. No changes in the interaction of pl-LDL with MAb 2G8 (residues 3748-4306) were observed in comparison with native LDL. This fact demonstrates that 50% phospholipolysis of LDL does not affect the expression of apo B C-terminal residues in pl-LDL. Twofold increase in pl-LDL affinity to immobilized LDL-receptor was shown in contrast to LDL. The data indicate that LPC accumulation in LDL results in better elimination of LDL from the blood stream than in case of accumulation of oxidative products.http://www.bibsonomy.org/bibtex/22bfc850dad7b18435795e81ad6b8e62f/biblio24biblio242006-07-07T01:10:50+02:00apob epitope mapping <span style="color:#555555;">R. J. <a href="http://www.bibsonomy.org/author/Pease">Pease</a> and R. W. <a href="http://www.bibsonomy.org/author/Milne">Milne</a> and W. K. <a href="http://www.bibsonomy.org/author/Jessup">Jessup</a> and A. <a href="http://www.bibsonomy.org/author/Law">Law</a> and P. <a href="http://www.bibsonomy.org/author/Provost">Provost</a> and J. C. <a href="http://www.bibsonomy.org/author/Fruchart">Fruchart</a> and R. T. <a href="http://www.bibsonomy.org/author/Dean">Dean</a> and Y. L. <a href="http://www.bibsonomy.org/author/Marcel">Marcel</a> and J. <a href="http://www.bibsonomy.org/author/Scott">Scott</a> </span><em>J Biol Chem</em><em>265(1):553--568</em><em>January1990. </em>Fri Jul 07 01:10:50 CEST 2006Division of Molecular Medicine, Medical Research Council Clinical Research Centre, Harrow, United Kingdom.J Biol ChemJanuary1553--568Use of bacterial expression cloning to localize the epitopes for a series of monoclonal antibodies against apolipoprotein B100.2651990apob epitope mapping Bacterial expression of apolipoprotein (apo) B cDNA constructs has been used to map a series of monoclonal antibodies (mAbs) to apoB by immunoblotting. In some cases assignments have been confirmed and refined by (i) semipurification of expressed protein, CNBr digestion, and assignment of the immunoreactive fragments; (ii) controlled digestion of the cDNA with the exonuclease Bal31 and bacterial expression of the truncated proteins that result; or (iii) expression of specific segments of cDNA amplified by the polymerase chain reaction. Forty mAbs were mapped to a minimum of 17 separate determinants on apoB. Tryptic fragments have been used to confirm the epitope assignments. In addition, this approach in conjunction with immunoassay, enables some deductions to be made about the trypsin-accessible regions in low density lipoprotein (LDL). The cleavage pattern obtained predicts retention of structure in the cysteine-rich domain of the amino terminus and also in the LDL receptor binding region. Trypsinized LDL was shown to bind to the LDL receptor by an authentic process, using monoclonal antibodies as competing ligands. In conjunction with the previous paper (Milne, R. W., Theolis, R., Maurice, R., Pease, R. J., Weech, P. K., Rassart, E., Fruchart, J.-C., Scott, J., and Marcel, Y. L. (1989) J. Biol. Chem. 265, 19754-19760) the mapped mAbs have been used to define the receptor-binding domain of apoB100 in LDL.http://www.bibsonomy.org/bibtex/27a4e0f35060731cfed390ca6cc428527/biblio24biblio242006-07-07T01:10:50+02:00epitope mapping apob <span style="color:#555555;">X. <a href="http://www.bibsonomy.org/author/Wang">Wang</a> and V. <a href="http://www.bibsonomy.org/author/Chauhan">Chauhan</a> and A. T. <a href="http://www.bibsonomy.org/author/Nguyen">Nguyen</a> and J. <a href="http://www.bibsonomy.org/author/Schultz">Schultz</a> and J. <a href="http://www.bibsonomy.org/author/Davignon">Davignon</a> and S. G. <a href="http://www.bibsonomy.org/author/Young">Young</a> and J. <a href="http://www.bibsonomy.org/author/Boren">Boren</a> and T. L. <a href="http://www.bibsonomy.org/author/Innerarity">Innerarity</a> and H. <a href="http://www.bibsonomy.org/author/Rutai">Rutai</a> and R. W. <a href="http://www.bibsonomy.org/author/Milne">Milne</a> </span><em>J Lipid Res</em><em>44(3):547--553</em><em>March2003. </em>Fri Jul 07 01:10:50 CEST 2006Lipoprotein and Atherosclerosis Research Group and the Department of Pathology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.J Lipid ResMarch3547--553Immunochemical evidence that human apoB differs when expressed in rodent versus human cells.442003epitope mapping apob LDL from human apolipoprotein B-100 (apoB-100) transgenic (HuBTg+/+) mice contains more triglyceride than LDL from normolipidemic subjects. To obtain novel monoclonal antibody (MAb) probes of apoB conformation, we generated hybridomas from HuBTg+/+ that had been immunized with LDL isolated from human plasma. One apoE-specific and four anti-apoB-100-specific hybridomas were identified. Two MAbs, 2E1 and 3D11, recognized an epitope in the amino-terminal 689 residues of apoB in native apoB-containing lipoproteins (LpBs) from human plasma or from the supernatant of human hepatoma HepG2 cells, but did not react with LpB from HuBTg+/+ mice or LpB secreted by human apoB-100-transfected rat McArdle 7777 hepatoma cells. 2E1 reacted weakly and 3D11 reacted strongly with apoB from HuBTg+/+ mice after SDS-PAGE. The lack of expression of the 2E1 and 3D11 epitopes on native LpB from HuBTg+/+ mice did not solely reflect the abnormal lipid composition of murine LpB. Both epitopes were detected in all human plasma samples tested and in all human plasma LpB classes. Therefore, human apoB expressed by rodent hepatocytes or hepatoma cells appears to adopt a different conformation or undergoes different posttranslational modification than apoB expressed in human hepatocytes or hepatoma cells.http://www.bibsonomy.org/bibtex/28a5794e6f329c353fcea2f5897cbd46b/biblio24biblio242006-07-07T01:10:50+02:00mapping apob epitope <span style="color:#555555;">A. <a href="http://www.bibsonomy.org/author/Corsini">Corsini</a> and S. <a href="http://www.bibsonomy.org/author/Fantappiè">Fantappi&#232;</a> and S. <a href="http://www.bibsonomy.org/author/Marcovina">Marcovina</a> and A. <a href="http://www.bibsonomy.org/author/Granata">Granata</a> and R. <a href="http://www.bibsonomy.org/author/Fumagalli">Fumagalli</a> and A. L. <a href="http://www.bibsonomy.org/author/Catapano">Catapano</a> </span><em>Biochem Biophys Res Commun</em><em>162(3):908--915</em><em>August1989. </em>Fri Jul 07 01:10:50 CEST 2006Institute of Pharmacological Sciences, University of Milan, Italy.Biochem Biophys Res CommunAugust3908--915Monoclonal antibody 5A binds apolipoprotein B-48 and inhibits the low density lipoprotein-receptor interaction.1621989mapping apob epitope In a panel of 10 monoclonal antibodies raised against human LDL we detected three antibodies (named 5A, 6B, and 6E) which recognize both apolipoprotein B-100 and B-48. Antibody 5A inhibited, in a dose dependent manner, the interaction of 125I-LDL with their receptor on human skin fibroblasts. Using thrombolytic fragments, the epitope of antibody 5A was mapped to the carboxy terminal region of apo B-48. MAB 5A was equipotent with MAB Mb 47, an inhibitory antibody whose epitope lies near a putative receptor binding domain of apo B in thrombolytic fragment T2. These findings suggest that areas other than the carboxy terminal portion of apo B-100 may participate in the LDL-receptor interaction, either directly or by determining the exposition of high affinity sites of apo B-100.http://www.bibsonomy.org/bibtex/20b3e46124d1770fa355cff318f616c3b/biblio24biblio242006-07-07T01:10:50+02:00mapping apob epitope <span style="color:#555555;">J. E. <a href="http://www.bibsonomy.org/author/Chatterton">Chatterton</a> and M. L. <a href="http://www.bibsonomy.org/author/Phillips">Phillips</a> and L. K. <a href="http://www.bibsonomy.org/author/Curtiss">Curtiss</a> and R. W. <a href="http://www.bibsonomy.org/author/Milne">Milne</a> and Y. L. <a href="http://www.bibsonomy.org/author/Marcel">Marcel</a> and V. N. <a href="http://www.bibsonomy.org/author/Schumaker">Schumaker</a> </span><em>The Journal of Biological Chemistry</em><em>266(9):5955--5962</em><em>March1991. </em>Fri Jul 07 01:10:50 CEST 2006Department of Chemistry and Biochemistry, University of California, Los Angeles 90024-1569.The Journal of Biological ChemistryMarch95955--5962Mapping apolipoprotein B on the low density lipoprotein surface by immunoelectron microscopy.2661991mapping apob epitope Apolipoprotein B (apoB) was mapped using electron microscopy to visualize pairs of monoclonal antibodies binding to the low density lipoprotein (LDL) surface. The sites at which these monoclonals bind the apoB polypeptide sequence had already been established. The angular distances between all possible pairs of binding sites except one allowed the relative placement of six epitopes on the LDL sphere. We conclude that apoB extends over at least a hemisphere of the LDL surface since four epitopes are located in the Northern Hemisphere at sites arbitrarily designated as the North Pole, the Aleutian Islands, Bogotá, and in the Atlantic Ocean, while two are found in the Southern Hemisphere at Buenos Aires and at Madagascar. ApoB appears to possess a restricted flexibility, since these relative epitope locations show a substantial standard deviation in latitude and longitude. Mapping of additional epitopes may provide an answer to the question of whether apoB circumnavigates the LDL sphere.