Enterotoxin residues determining T-cell receptor Vβ binding specificity

Abstract

SUPERANTIGENS such as the staphylococcal enterotoxins bind to major histocompatibility complex (MHC) class II molecules and activate T cells through a specific interaction between the V/β region of the T-cell antigen receptor (TCR) and the toxin^1–4. The TCR β-chain alone is sufficient to produce the interaction with the enterotoxin–class II complex⁵. Identification of the regions of enterotoxins that interact with TCR has so far proved equivocal because of difficulties in distinguishing between direct effects on T-cell recognition and indirect effects resulting from alteration of binding to class II. For example, amino-terminal truncations of SEB abrogated T-cell stimulation whereas carboxy-terminal truncation of SEA stopped its mitogenic activity^10,11. The most comprehensive study to date, accounting for both enterotoxin binding to class II and enterotoxin interactions with the TCR, identified two functionally important regions for SEB binding to TCR¹². Although the amino-acid sequences of staphylococcal enterotoxins A and E are 82% identical6, they activate T cells bearing different Vβ elements. We have assayed the binding of cells coated with these enterotoxins to soluble secreted TCR β-chain protein and find that Vβ3 binds enterotoxin A but not E, whereas Vβ11 binds enterotoxin but not A. To map the amino-acid residues responsible for these different binding specificities, we prepared a series of hybrids between the two staphylococcal enterotoxins. We report that just two amino-acid residues near the carboxy terminus of the enterotoxins are responsible for the dis-crimination between these molecules by Vβ3 and Vβ11. The crystal structure of staphylococcal enterotoxin B (ref. 12) indicates that these form part of the outer rim of the site recognizing TCR.