title: Mutational analysis and molecular modeling of the binding of Staphylococcus aureus enterotoxin C2 to a murine T cell receptor Vbeta10 chain.
abstract: We investigated the role of the beta chain HV4 region in the binding of a Vbeta10 T cell receptor to superantigen S. aureus enterotoxin C2 (SEC2)/MHC class II complexes. Residues 6971 of the Cw3/1.1 TCR Vbeta10 chain, derived from an H-2K(d)-restricted cytotoxic clone, were individually changed to alanine using site-directed mutagenesis, and mutated TCR beta chains were transfected along with the wild-type TCR alpha chain into a TCR alpha(-)beta(-) T hybridoma. SEC2/MHC recognition was measured by IL-2 production. Alanine substitutions in the HV4beta region, either did not affect (Ser69 and Lys71), or increased the recognition of SEC2/HLA-DR1 complex (Asp70), arguing against a general and direct role for the HV4beta region in superantigenrecognition. A theoretical-computational model of the SEC2/TCR Vbeta10 chain complex was constructed and predicted the presence of a unique salt bridge between Vbeta Asp30 and SEC2 Lys103. A perfect correlation was found between the likely presence of this salt bridge and the capacity of the HV4beta and previously obtained CDR1beta alanine mutants to induce an equal or greater response than the wild-type TCR.
authors.affiliation: Instituto de Biofísica Carlos Chagas F degrees, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
authors.forename: Shaila C
authors.initials: SC
authors.lastname: Rössle
authors.forename: Paulo M
authors.initials: PM
authors.lastname: Bisch
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lone
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Abastado
authors.forename: Philippe
authors.initials: P
authors.lastname: Kourilsky
authors.forename: Maria
authors.initials: M
authors.lastname: Bellio
mesh_terms: D000818:Animals; D001665:Binding Sites; D004768:Enterotoxins / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D013329:Structure-Activity Relationship; D018089:Superantigens / Q000276:immunology
chemical_list: D004768:Enterotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C034959:enterotoxin C, staphylococcal