DEGENERATE ANTIGEN RECOGNITION BY CD4(-CELLS IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS() EFFECTOR T)

Peptide-specific tolerance with PLP139-151 peptide analogs was used to compare the fine antigen-specificity requirements at both the inducti ve and effector phases of relapsing EAE (R-EAE). A PLP139-151 analog p eptide containing a single substitution at the primary T cell receptor (TcR) contact residue (A144) did not induct proliferation in PLP139-1 51-primed CD4+ T cells. In addition, tolerance induced with ECDI-treat ed, A144-coupled splenocytes failed to prevent the inductive phase of PLP139-151-induced R-EAE or to inhibit the induction of peptide-specif ic DTH indicating that naive PLP139-151-specific T cells do not react with the A144 peptide analog, In contrast, A144-coupled splenocytes di d prevent the expression of the effector phase of R-EAE and inhibited the elicitation of peptide-specific DTH responses upon administration to mice seven days after immunization with PLP139-151, The results pro vide in vivo evidence that 'antigen-experienced' T cells recognize a b roader repertoire of antigens than do naive T cells and have important implications for the regulation of immune responses and for advancing our understanding of the pathogenesis and treatment of autoimmune dis ease.