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

• Published in: The Journal of immunology (1950) Vol. 157; no. 9; pp. 3988 - 3994
• Main Authors: Newton, D W, Dohlsten, M, Olsson, C, Segren, S, Lundin, KEA, Lando, P A, Kalland, T, Kotb, M
• Format: Journal Article
• Language: English
• Published: 01.11.1996
• Subjects: Staphylococcus
• ISSN: 0022-1767

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, including F47, are involved in low affinity binding to MHC class II alpha -chain. The effect of alanine substitutions at residues D227 or F47 on induction of T cell proliferation and the expansion of specific TCR V beta families was determined. SEA wild type specifically activated T cells expressing V beta 1, V beta 5.2, V beta 6, V beta 7, V beta 9, V beta 18, and V beta 22. Although SEA-D227A exhibited substantially reduced mitogenicity compared with SEA wild type, it expanded the same V beta -bearing T cells, except those expressing V beta 1. By contrast, SEA-F47A, which was slightly less mitogenic than SEA wild type, induced expansion only of T cells expressing V beta 6, V beta 7, and to a lesser extent V beta 22. Therefore, specific mutations affecting either MHC class II alpha or beta binding sites differentially affect the V beta specificity of this superantigen. The lack of expansion in four of seven V beta families by SEA-F47A suggests that the class II alpha binding site may position SEA on the MHC class II molecules in an appropriate conformation for interaction with certain V beta elements.