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Subtype‐specific interactions of type C staphylococcal enterotoxins with the T‐cell receptor
Author(s) -
Deringer James R.,
Ely R. James,
Stauffacher Cynthia V.,
Bohach Gregory A.
Publication year - 1996
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.1996.1381506.x
Subject(s) - t cell receptor , biology , complementarity determining region , superantigen , microbiology and biotechnology , beta (programming language) , hypervariable region , receptor , mutant , peptide sequence , t cell , antibody , biochemistry , genetics , gene , immune system , computer science , programming language
The goal of this study was to investigate the molecular interaction between superantigens and the T‐cell receptor (TCR). Using a quantitative polymerase chain reaction (PCR) to assess T‐cell proliferation profiles, we found that SEB, SEC1, SEC2 and SEC3 expanded human T cells bearing Vβ3, Vβ12, Vβ13.2, Vβ14, Vβ15, Vβ17 and Vβ20. SEC2 and SEC3 have the additional ability to expand T cells bearing Vβ13.1, and their expansion of Vβ3 was markedly reduced compared to SEB and SEC1. Based on the activity of SEC1 mutants containing single amino acid substitutions, we concluded that the differential abilities of these native toxins to stimulate Vβ3 and Vβ13.1 was determined by the residue in position 26, located in the base of the SEC α3 cavity. The SEC1 mutant, in which Val in position 26 was substituted with the analogous SEC2/SEC3 residue (Tyr), generated a Vβ expansion profile that was indistinguishable from those generated by SEC2 and SEC3. Using these findings, the co‐ordinates of a recently reported murine TCR β‐chain crystal structure, and other documented information, we propose a compatible molecular model for the interaction of SEC3 with the T‐cell receptor. In this model complex, the complementarity‐determining regions (CDRs) 1 and 2 and the hypervariable loop 4 of the Vβ element contact SEC3 predominantly through residues in the α3 cavity of the toxin. CDR3 of the β chain is not involved in any toxin contacts. The proposed model not only includes contacts identified in previous mutagenesis studies, but is also consistent with the ability of tyrosine and valine in position 26 to differentially affect the expansion of Vβs 3 and 13.1 by the SEC superantigens.