Encephalitogenic T cell clones with variant receptor specificity

We explored antigenic differences between guinea pig (GP)-basic protein (BP), rat (Rt)-BP, and respective peptides from the encephalitogenic region for Lewis rats by comparing the fine specificity of T lymphocyte lines and clones selected from animals primed with these Ag. Encephalitogenic T cell lines specific for GP-BP or Rt-BP predictably recognized the corresponding 72-89 and to a lesser degree the 72-84 (S55S) amino acid sequence. T cell lines selected from rats primed with GP-S55S responded preferentially to GP-S55S compared to other peptides. A T cell line raised to Rt-S55S, however, initially recognized the S55S and S72-89 peptides but were nearly unresponsive to the intact GP-BP or Rt-BP. T cell clones selected from the Rt-S55S line at that point had two distinct patterns of response: clones that recognized both of the BP and the S55S peptides adoptively transferred delayed-type hypersensitivity and experimental autoimmune encephalomyelitis. These clones also recognized residues 69-81 (S67) but not peptide S75-89. In contrast, T cell clones that responded only to synthetic peptides GP-S55S and Rt-S55S but not to the parent BP adoptively transferred delayed-type hypersensitivity but not disease in Lewis rats. The same clones failed to respond to either the S67 or the S75-89 sequences. These results demonstrate that the encephalitogenic Rt-S55S sequence houses a minimum of two T cell epitopes with differing specificities and functions. One epitope is immuno-dominant and resembles the encephalitogenic region of the intact BP molecule. The second non-encephalitogenic epitope is restricted to the S55S sequences and is not shared by the parent BP, the S67, or the S75-89 sequences. Both types of Rt-S55S-specific clones differ in fine specificity from encephalitogenic clones selected from GP-BP immunized rats, thus indicating that uniformity of T cell recognition of the encephalitogenic epitope is not an absolute condition for T cells to be encephalitogenic.