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

Abstract

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 micrograms/ml. The 69-84 and 72-84 sequences induced comparable levels of stimulation at 250 micrograms/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.