The sites of antigen-T cell and antigen-MHC interactions overlap.

The immune responses of B10.A and B10.A(3R) strains of mice to a synthetic variant of moth cytochrome c 86-103 were compared, and an immune response difference between the two strains was found. When T cell hybridomas were made from both strains it was found that the responsive T cells showed degenerate MHC restriction. The hybridomas from B10.A(3R) mice consistently showed a specificity pattern, when tested with allogeneic B10.A APC, different from that seen when syngeneic B10.A(3R) APC were used. The difference in the immune responses of the two strains of mice could be attributed to this APC-expressed specificity. The results were analyzed to determine whether the portion of the antigen that effected T cell memory (the epitope) and the portion that effected APC-expressed specificity (the agretope) were independent. It was found that a) these sites overlap and b) the APC-expressed specificity (i.e., the specificity of agretope recognition) was dependent on the T cell clonotype. This implies that the agretope is not an independent parameter in the process of MHC-restricted antigen recognition. Therefore its employment as an explanation for various phenomena will be limited by the likelihood of circularity.