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.
%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
}