Residues of the variable region of the T-cell-receptor β-chain that interact with S. aureus toxin superantigens

Abstract

The alpha beta T-cell antigen receptor (TCR) recognizes antigenic peptides in the context of self major histocompatibility complex (MHC) molecules. The specificity of recognition of MHC plus antigen is generally determined by a combination of the variable elements of alpha- and beta-chains of the TCR. Several types of antigen, however, have been identified that, when bound to MHC molecules, stimulate T cells bearing particular variable-region beta-chain (V beta) elements irrespective of the other variable components of the TCR. These have been termed 'superantigens', and here we are concerned with one type of superantigen, the toxins produced by Staphylococcus aureus. T cells have been found that bear closely related members of the same V beta family but respond differently to S. aureus toxins; in particular, cells bearing the human V beta 13.2 element respond to toxin SEC2, whereas cells bearing human V beta 13.1 do not. We have now defined the residues of the V beta element responsible for this difference, and find that they reside in a region thought to lie on the side of the TCR molecule, away from the conventional antigen/MHC-binding site. The evolutionary conservation of this site may be due to its having an important role in some function of the TCR other than the binding of conventional antigen plus MHC.

A method for production of antibodies to human T-cell receptor beta-chain variable regions.

“…Transfection of Mouse T-Hybridoma Cells. An expression vector carrying the appropriate hVO genes was transfected by electroporation into a mouse T-cell hybridoma (DS23-27.4) that lacked endogenous TCR 3-chain genes (31). Transfected cells were selected with G418 (700,ug/ml) as described (31).…”

“…In brief, TCR (3 genes were constructed using a gene fragment encoding the Dp, Jp3, and Cp. elements of a mouse T-cell hybridoma gene (31) and the Vp genes encoding human Vl13.1 or -13.2. The Vp genetic elements were created by PCR of the cDNA from human T-cell mRNA, using Vpspecific oligonucleotides as primers.…”

Staphylococcal scalded skin syndrome

“…66 A conventional antigen is normally processed initially by an antigen-presenting cell, such as a macrophage, which then presents the antigen at the cell surface within a groove of the MHC class I1 molecule. This complex is recognised by a small number (1 in c. lo6) of T cells which bear specific receptors for this antigen.…”

Direct binding of secreted T-cell receptor beta chain to superantigen associated with class II major histocompatibility complex protein.

“…This is supported by recent experiments showing the importance ofthe fourth hypervariable region of Vp in superantigen recognition (21,22). To test whether the p chain is sufficient for the interaction we have used a soluble TCR p chain protein expressed from a truncated gene lacking a transmembrane segment (23).…”