2 ADJACENT RESIDUES IN STAPHYLOCOCCAL ENTEROTOXIN-A AND ENTEROTOXIN-E DETERMINE T-CELL RECEPTOR V-BETA-SPECIFICITY

The T cell receptor (TCR) Vbeta-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 Vbeta mRNA enrichment in human peripheral blood T cell cultures was determined by a navel single-tube amplification technique using a redundant Vbeta-specific primer. SEA routinely enriched mRNA coding for hVbeta1.1, 5.3, 6.3, 6.4, 6.9, 7.3, 7.4, and 9.1, while SEE, which is 83% homologous to SEA, enriched hVbeta5.1, 6.3, 6.4, 6.9, and 8.1 mRNA. Exchanging residues 206 and 207 was sufficient to convert in toto the TCR Vbeta response of human peripheral T lymphocytes. In addition, an SEA-reactive murine T cell line, SO3 (mVbeta17), unresponsive to wild-type SEE responded to SEE-S206N207, while an SEE-specific human T cell line, Jurkat (hVbeta8.1), 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 Vbeta response. Thus, the Vbeta 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 Vbeta.