T cell epitopes in experimental autoimmune myasthenia gravis of the rat: strain-specific epitopes and cross-reaction between two distinct segments of the alpha chain of the nicotinic acetylcholine receptor (Torpedo californica)

Abstract

T cell epitopes on the nicotinic acetylcholine receptor (A ChR) of Torpedo californica were analyzed using T cell lines isolated from Lewis, BN, and (Lewis X BN)F1 rats. All lines selected for reactivity against either native or denatured AChR or for 6 selected synthetic peptides of the AChR alpha chain expressed the CD4 membrane phenotype and recognized their antigen in the context of major histocompatibility complex class II determinants. They were tested in vitro for reactivity with each of these antigens. The results indicate that parental Lewis and BN rat T lymphocytes recognize distinct molecular epitopes on the AChR protein, whereas (Lewis X BN)F1 hybrids respond against both sets of epitopes. Two peptides (P10 and P11) which represent distinct amino acid sequences on the putatively extracellular part of the AChR alpha chain, and which share only 4 common amino acids, two of them contiguous, showed an unexpected cross-reactivity in the Lewis rat. T cells selected for either peptide co-recognize the other peptide in vitro. In addition, these cells are responsive against full length AChR. P11, in particular, appears to be a major epitope for Lewis rats immunized with AChR.