Response of rat encephalitogenic T lymphocyte lines to synthetic peptides of myelin basic protein

T lymphocyte lines and clones selected from Lewis rats immunized with guinea pig basic protein (GP‐BP) proliferate and acquire the ability to transfer experimental autoimmune encephalomyelitis (EAE) after activation by the 68–88 peptide of GP‐BP in concert with autologous I‐A major histocompatibility antigens. In order to evaluate the amino acid sequence required for activation, encephalitogenic T lymphocytes were stimulated with synthetic peptides representing the 69–89, 69–84, 72–84, and 75–84 sequence of GP‐BP. The three longest peptides, but not the 75–84 peptide, induced encephalitogenic lines and clones to proliferate and to transfer clinical EAE; none of the peptides, however, could activate T cell lines of a different epitope specificity. The 69–89 sequence was the most efficient of the synthetic peptides, inducing optimal stimulation comparable to GP‐BP at 10 μg/ml. The 69–84 and 72–84 sequences induced comparable levels of stimulation at 250 μg/ml, but the 75–84 sequence was not active at any concentration. These results show that the 11 amino acids representing the 72–84 sequence of GP‐BP are sufficient to trigger encephalitogenic T cell activity, and suggest that the 85–89 sequence may stabilize the conformation of the encephalitogenic epitope. The close association observed between proliferation and EAE transfer activities, induced in highly purified T cell populations using synthetic peptides, suggests that these two functional properties of T cells result from a common activation pathway involving a single T cell receptor specificity.