Mutations in the MHC class II binding domains of staphylococcal enterotoxin A differentially affect T cell receptor Vbeta specificity.

摘要: C-terminal residues of staphylococcal enterotoxin A (SEA), including H187, D225, and D227, are involved in moderate affinity binding to MHC class II beta-chain, whereas N-terminal residues, F47, low alpha-chain. The effect alanine substitutions at D227 or F47 on induction T cell proliferation the expansion specific TCR Vbeta families was determined. SEA wild type specifically activated cells expressing Vbeta1, Vbeta5.2, Vbeta6, Vbeta7, Vbeta9, Vbeta18, Vbeta22. Although SEA-D227A exhibited substantially reduced mitogenicity compared with type, it expanded same Vbeta-bearing cells, except those Vbeta1. By contrast, SEA-F47A, which slightly less mitogenic than induced only a lesser extent Therefore, mutations affecting either alpha beta sites differentially affect specificity this superantigen. lack four seven by SEA-F47A suggests that site may position molecules an appropriate conformation for interaction certain elements.