Immunization of mice with nicotinic acetylcholine receptor from Torpedo electric organ (TAChR) causes a disease similar to human myasthenia gravis (experimental autoimmune myasthenia gravis, EAMG). Susceptibility to EAMG correlates with the H‐2 haplotype. In this study we used overlapping synthetic peptide corresponding to the complete sequences of the α subunits from TAChR and murine muscle AChR (MAChR) to map T helper epitopes in congenic murine strains of different H‐2 haplotype. C57BL/6 and BALB/B mice (highly susceptible to EAMG) and BALB/c and CB17 mice (less susceptible to EAMG), immunized with TAChR, developed similar anti‐TAChR antibody titers and L3T4⁺ (T helper) cell sensitization. Different sequence segments of the TAChR α subunit were recognized by L3T4⁺ cells from strains of H‐2^b and H‐2^d haplotype. The sequence segments recognized by the H‐2^d strains have the highest predicted propensity to form amphipatic α helices, while those recognized by the H‐2^b strains do not.

We investigated whether in EAMG T helper cells cross‐react with autologous AChR sequences, and a true break of the tolerance occurs. Overlapping synthetic peptides, corresponding to the complete sequence of MAChR α subunit, were used to test L3T4⁺ cell from mice immunized with TAChR. L3T4⁺ cell from H‐2^b strains did not cross‐react with any murine peptide sequence, while L3T4⁺ cells from H‐2^d mice were strongly stimulated by the peptide sequence Mα 304‐322, which is very similar to the homologous Torpedo peptide.