Degenerate recognition of a dissimilar antigenic peptide by myelin basic protein-reactive T cells. Implications for thymic education and autoimmunity.

The key event in the induction of an immune response is the recognition by a T lymphocyte of an antigenic peptide bound to a MHC molecule. In the absence of structural coordinates of the TCR and class II MHC molecules, various models of T cell recognition have been proposed, with the emerging dogma that T cell recognition is exquisitely specific. We show here that T cell clones specific for the N-terminal fragment of myelin basic protein, acetylated Ac1-11, recognize a set of unrelated peptides in the context of the same I-Au molecule. Moreover, immunization with the peptide mimic is sufficiently cross-reactive with Ac1-9 to either induce the Ac1-9-reactive clones or to induce tolerance as well as protection against Ac1-9-induced EAE. This observed degeneracy in T cell recognition has important implications for thymic selection and induction of autoimmune disease states by "molecular mimicry."