Inhibition of superantigen recognition by peptides of the variable region of the T cell receptor beta chain.

T cells bearing certain variable (V) regions of the T cell receptor (TcR), including V beta 3, V beta 6, V beta 8.1 and V beta 9, are stimulated by one or more forms of the endogenous superantigen, mouse lymphocyte stimulatory (Mls) locus, encoded by the mouse mammary tumor virus, in the context of a non-polymorphic region of the class II molecules of the major histocompatibility complex (MHC). To identify putative sites of interaction of TcR-V beta region and Mls-1a, we examined the effect of peptides derived from the protein sequence of V beta 6 on recognition of Mls-1a by T cell hybridomas and show that three peptides corresponding to amino acid positions 1 to 20, 48 to 75, and 58 to 75 of the V beta 6 peptide sequence interfere with the activation of several V beta 6+ hybridomas by Mls-1a-bearing spleen cells, but not with that of a V beta 8+ hybridoma. The Mls-reactive hybridomas are specific for a synthetic peptide poly-18, poly EYK(EYA)5 and its peptide (EYA)5, in the context of I-Ad. This peptide does not require processing and the peptides 1-20, 48-75, and 58-75 do not inhibit recognition of (EYA)5 by the same V beta 6+ T cell hybridomas. The two sequences 1-20 and 58-75 are proposed to lie outside the putative binding domain of processed antigen, indicating that recognition by TcR of Mls-1a is different from the classical MHC-restricted recognition of processed antigen. These results suggest that the recognition of superantigen/class II MHC by T cells can be inhibited by peptides related to the site of interaction of the TcR, suggesting that such peptides could have possible regulatory effects on the induction and regulation of immune responses.