T-CELL RESPONSES IN EAMG-SUSCEPTIBLE AND NON-SUSCEPTIBLE MOUSE STRAINS AFTER IMMUNIZATION WITH OVERLAPPING PEPTIDES ENCOMPASSING THE EXTRACELLULAR PART OF TORPEDO-CALIFORNICA ACETYLCHOLINE-RECEPTOR ALPHA-CHAIN- IMPLICATION TO ROLE IN MYASTHENIA-GRAVIS OF AUTOIMMUNE T-CELL RESPONSES AGAINST RECEPTOR DEGRADATION PRODUCTS

To study the role in myasthenia gravis (MG) of peptides resulting from acetylcholine receptor (AChR) degradation, we examined the ability of AChR peptides to induce T sell responses that are capable of cross-re acting with intact AChR. The studies were carried out in an experiment al autoimmune MG (EAMG)-susceptible mouse strain [C57BL/6 (B6)] as wel l as in two non-susceptible strains [B6.C-H-2(bm12) (bm12) and C3H/He] . A set of overlapping peptides encompassing the extracellular part (r esidues 1-210) of the alpha-chain of Torpedo californica (t) AChR were used, individually or in equimolar mixtures, as immunogens. In B6, im munization with peptides alpha 45-60, alpha 111-126, alpha 146-162 and alpha 182-198 gave T cells that responded in vitro to the correlate i mmunizing peptide. Only the T cells against the latter three peptides cross-reacted with tAChR. Peptide alpha 146-162 exhibited the highest in vitro reaction with the immunizing peptide and cross-reaction with tAChR. T cells obtained by immunization of B6 with an equimolar mixtur e of the peptides responded in vitro to peptides alpha 111-126, alpha 146-162 and alpha 182-198 and cross-reacted very strongly with tAChR. In bm12 and C3H/He, a number of peptides evoked, when used individuall y as immunogens, strong or moderate T cell responses that recognized i n vitro the correlate immunizing peptide but cross-reacted poorly with tAChR. Immunization with the mixture of the peptides gave T cells tha t recognized several peptides in each strain but did not cross-react w ith alpha 146-162 or tAChR. The results indicate that the ability to r ecognize alpha 146-162 or AChR by T cells against peptides resulting f rom receptor degradation can account for the susceptibility to, and ag gravation of, MG in B6.