T Cell Epitopes of the Acetylcholine Receptor and the Pathogenesis of Myasthenia Gravis
CD4-positive T cells are required for sustained antibody production. T and B lymphocytes recognize cognate determinants of an antigen and communicate by direct cell to cell interactions including the CD40/CD40-ligand and B7-CTLA4 pairs of accessory molecules (reviewed in Clark and Ledbetter, 1994). In addition, T cell derived cytokines promote growth and differentiation signals for antibody-producing B cells (Coffman et al., 1988). In the animal model of myasthenia gravis (MG), experimental autoimmune myasthenia gravis (EAMG), the depletion of T lymphocytes prevents the production of autoantibodies after immunization with acetylcholine receptor (AChR; Lennon et al., 1976). T helper cells recognize antigen in the context of MHC class II molecules. Inhibition of antigen recognition by monoclonal antibodies to MHC class II molecules has been reported to suppress the immune response to AChR and prevent EAMG in vivo (Waldor et al., 1983). MHC class II molecules bind peptides in a preformed binding groove and allelic products differ in their binding requirements which have been described as allele-specific ligand or binding motifs (Rammensee et al., 1995). For example, the bm-12 mutation of murine MHC class II molecules I-A alters the peptide binding site of MHC class II molecules, hence, animals with the bm-12 mutation respond to a different set of AChR peptides compared to the wild type and are resistant to the induction of EAMG (Bellone et al., 1991). This underscores the strong influnence of MHC class II molecules on the determinant selection and the immune response regarding the susceptibility to develop an autoimmune disease.
KeywordsAcetylcholine Receptor Cell Epitope Tetanus Toxin Nicotinic Receptor Alpha Binding Requirement
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