Two adjacent residues in staphylococcal enterotoxins A and E determine T cell receptor Vβ specificity

Abstract

The T cell receptor (TCR) Vβ-determining region of two bacterial superantigens, staphylococcal enterotoxin A (SEA) and SEE, has been mapped to the COOH-terminal region of SEA and SEE using a panel of recombinant SEA/SEE hybrids. Total TCR Vβ mRNA enrichment in human peripheral blood T cell cultures was determined by a novel single-tube amplification technique using a redundant Vβ-specific primer. SEA routinely enriched mRNA coding for hVβ1.1, 5.3, 6.3, 6.4, 6.9, 7.3, 7.4, and 9.1, while SEE, which is 83% homologous to SEA, enriched hVβ5.1, 6.3, 6.4, 6.9, and 8.1 mRNA. Exchanging residues 206 and 207 was sufficient to convert in toto the TCR Vβ response of human peripheral T lymphocytes. In addition, an SEA-reactive murine T cell line, SO3 (mVβ17), unresponsive to wild-type SEE responded to SEE-S206N207, while an SEE-specific human T cell line, Jurkat (hVβ8.1), unresponsive to SEA was stimulated strongly by SEA-P206D207. Exchanging all other regions of SEA and SEE except residues 206 and 207 did little to change the Vβ response. Thus, the Vβ binding region appears to be a stable, discrete domain localized within the COOH-terminal region that is largely unaffected by the considerable amino acid variability between SEA and SEE. This region may interact directly with TCR Vβ.