title: Different superantigens interact with distinct sites in the Vbeta domain of a single T cell receptor.
abstract: CD4 T cell receptors (TCRs) recognize antigenic peptides presented by self major histocompatibility complex (MHC) class II molecules as well as non-self MHC class II molecules. The TCRs can also recognize endogenous retroviral gene products and bacterial toxins known collectively as superantigens (SAGs) that act mainly on the Vbeta gene segment-encoded portion of the Vbeta domain; most SAGs also require MHC II class for presentation. We have studied the interaction of the TCR from a well-characterized CD4 T cell line with SAGs by mutational analysis of its Vbeta domain. This appears to separate viral (v)SAG from bacterial (b)SAG recognition. T cells having a TCR with glycine to valine mutation in amino acid residue 51 (G51V) in complementarity determining region 2 of the TCR Vbeta domain fail to respond the bSAGs staphylococcal enterotoxin B (SEB), SEC1, SEC2, and SEC3, whereas they retain the ability to respond to non-self MHC class II molecules and to foreign peptides presented by self MHC class II molecules. It is interesting to note that T cells expressing mutations of both G51V and G53D of V beta regain the response to SEB and partially that to SEC1, but do not respond to SEC2, and SEC3, suggesting that different bacterial SAGs are viewed differently by the same TCR. These results are surprising, because it has been generally believed that SAG recognition by T cells is mediated exclusively by hypervariable region 4 on the exposed, lateral face of the TCR Vbeta domain. Response to the vSAG Mtv-7 was generated by mutation in Vbeta residue 24 (N24H), confirming previously published data. These data show that the vSAG Mtv-7 and bSAGs are recognized by different regions of the TCR Vbeta domain. In addition, various bSAGs are recognized differently by the same TCR. Thus, these mutational data, combined with the crystal structure of the TCR beta chain, provide evidence for distinct recognition sites for vSAG and bSAG.
authors.affiliation: Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Hong
authors.forename: G
authors.initials: G
authors.lastname: Waterbury
authors.forename: C A
authors.initials: CA
authors.lastname: Janeway
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004252:DNA Mutational Analysis; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011485:Protein Binding; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism*; D018089:Superantigens / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
chemical_list: D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens