%0 Journal Article %1 Protti1992 %A Protti, M. P. %A Manfredi, A. A. %A Wu, X. D. %A Moiola, L. %A Dalton, M. W. %A Howard, J. F. %A Conti-Tronconi, B. M. %D 1992 %J J Clin Invest %K Acid Adult; Aged; Amino Antigens, CD4-Positive Cell Cholinergic, Data; Epitopes; Female; Gravis, HLA-DR Humans; Line; Male; Middle Molecular Muscles, Myasthenia Receptors, Sequence Sequence; T-Lymphocytes, embryology/immunology; genetics; immunology immunology; %N 4 %P 1558--1567 %R 10.1172/JCI116024 %T Myasthenia gravis. CD4+ T epitopes on the embryonic gamma subunit of human muscle acetylcholine receptor. %U http://dx.doi.org/10.1172/JCI116024 %V 90 %X In myasthenia gravis (MG) an autoimmune response against muscle acetylcholine receptor (AChR) occurs. Embryonic muscle AChR contains a gamma subunit, substituted in adult muscle by a homologous epsilon subunit. Antibodies and CD4+ cells specific for embryonic AChR have been demonstrated in MG patients. We identified sequence segments of the human gamma subunit forming epitopes recognized by four embryonic AChR-specific CD4+ T cell lines, propagated from MG patients' blood by stimulation with synthetic peptides corresponding to the human gamma subunit sequence. Each line had an individual epitope repertoire, but two 20-residue sequence regions were recognized by three lines of different HLA haplotype. Most T epitope sequences were highly diverged between the gamma and the other AChR subunits, confirming the specificity of the T cells for embryonic AChR. These T cells may have been sensitized against AChR expressed by a tissue other than innervated skeletal muscle, possibly the thymus, which expresses an embryonic muscle AChR-like protein, containing a gamma subunit. Several sequence segments forming T epitopes are similar to regions of microbial and/or mammalian proteins unrelated to the AChR. These findings are consistent with the possibility that T cell cross-reactivity between unrelated proteins ("molecular mimicry"), proposed as a cause of autoimmune responses, is not a rare event.

@article{Protti1992, __markedentry = {[mdalton]}, abstract = {In myasthenia gravis (MG) an autoimmune response against muscle acetylcholine receptor (AChR) occurs. Embryonic muscle AChR contains a gamma subunit, substituted in adult muscle by a homologous epsilon subunit. Antibodies and CD4+ cells specific for embryonic AChR have been demonstrated in MG patients. We identified sequence segments of the human gamma subunit forming epitopes recognized by four embryonic AChR-specific CD4+ T cell lines, propagated from MG patients' blood by stimulation with synthetic peptides corresponding to the human gamma subunit sequence. Each line had an individual epitope repertoire, but two 20-residue sequence regions were recognized by three lines of different HLA haplotype. Most T epitope sequences were highly diverged between the gamma and the other AChR subunits, confirming the specificity of the T cells for embryonic AChR. These T cells may have been sensitized against AChR expressed by a tissue other than innervated skeletal muscle, possibly the thymus, which expresses an embryonic muscle AChR-like protein, containing a gamma subunit. Several sequence segments forming T epitopes are similar to regions of microbial and/or mammalian proteins unrelated to the AChR. These findings are consistent with the possibility that T cell cross-reactivity between unrelated proteins ("molecular mimicry"), proposed as a cause of autoimmune responses, is not a rare event.}, added-at = {2010-06-02T20:45:31.000+0200}, author = {Protti, M. P. and Manfredi, A. A. and Wu, X. D. and Moiola, L. and Dalton, M. W. and Howard, J. F. and Conti-Tronconi, B. M.}, biburl = {https://www.bibsonomy.org/bibtex/26fa4c3e7ab3663257321e393f27b5cfb/markwdalton}, description = {Marks Publications}, doi = {10.1172/JCI116024}, institution = {Department of Biochemistry, College of Biological Sciences, University of Minnesota, St. Paul 55108.}, interhash = {abb81b93a8eedb14066d01149c5b2179}, intrahash = {6fa4c3e7ab3663257321e393f27b5cfb}, journal = {J Clin Invest}, keywords = {Acid Adult; Aged; Amino Antigens, CD4-Positive Cell Cholinergic, Data; Epitopes; Female; Gravis, HLA-DR Humans; Line; Male; Middle Molecular Muscles, Myasthenia Receptors, Sequence Sequence; T-Lymphocytes, embryology/immunology; genetics; immunology immunology;}, language = {eng}, medline-pst = {ppublish}, month = Oct, number = 4, owner = {mdalton}, pages = {1558--1567}, pmid = {1383275}, timestamp = {2010-06-02T20:45:32.000+0200}, title = {Myasthenia gravis. CD4+ T epitopes on the embryonic gamma subunit of human muscle acetylcholine receptor.}, url = {http://dx.doi.org/10.1172/JCI116024}, volume = 90, year = 1992 }