Studies from this laboratory have mapped and synthesized the functional (i.e. acetylcholine and α-neurotoxin binding) sites as well as the sites of immune and autoimmune T- and B-cell recognition of
Torpedo californica (
t) and human acetylcholine receptor (AChR). Antibodies against
tAChR and mouse (
m) AChR α-chain peptides have been used to map the surface accessibility of the α-chain extracellular domain in soluble (i.e. free) and in membrane-bound
tAChR as well as in
mAChR on a live muscle cell line in culture. Myasthenia gravis is a disease caused by autoantibodies against AChR. Yet, we have found on the molecule a pathogenic T-cell epitope which does not bind anti-AChR antibodies. It has been shown, for the first time, that T cells which recognize this region of the receptor to which no autoantibodies are detectable are pathogenic because they provide help to, and activate, B cells that make antibodies against a region of the molecule known to be involved in the binding of the effector moleucule. We have also performed studies, which have been quite successful, on the manipulation of the autoimmune antibody and T cell responses by synthetic peptides. These studies should open up important avenues for the use of synthetic peptides in the manipulation and control of unwanted immune responses.
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