Crystal structure of a T-cell receptor â chain complexed with a superantigen.

FIELDS BA, MALCHIODI EL, HONGMIN L, YSERN X, STAUFFACHER CV, SCHLIEVERT PM, KARJALAINEN K, MARIUZZA RA. FIELDS AND MALCHIODI CONTRIBUTED EQUALLY.

NATURE

Año: 1996 vol. 384 p. 188 - 192

0028-0836

Superantigens (SAgs) are viral or bacterial proteins that act as potent T-cellstimulants and have been implicated in a number of human diseases, includingtoxic shock syndrome, diabetes mellitus and multiple sclerosis. The interactionof SAgs with the T-cell receptor (TCR) and major histocompatibility complex (MHC)proteins results in the stimulation of a disproportionately large fraction of theT-cell population. We report here the crystal structures of the beta-chain of aTCR complexed with the Staphylococcus aureus enterotoxins C2 and C3 (SEC2, SEC3).These enterotoxins, which cause both toxic shock and food poisoning, bind in anidentical way to the TCR beta-chain. The complementarity-determining region 2(CDR2) of the beta-chain and, to lesser extents, CDR1 and hypervariable region 4 (HV4), bind in a cleft between the two domains of the SAgs. Thus, there isconsiderable overlap between the SAg-binding site and the peptide/MHC-bindingsites of the TCR. A model of a TCR-SAg-MHC complex constructed from the crystalstructures of (1) the beta-chain-SEC3 complex, (2) a complex betweenstaphylococcal enterotoxin B (SEB) and an MHC molecule, and (3) a TCR V(alpha)domain, reveals that the SAg acts as a wedge between the TCR and MHC to displace the antigenic peptide away from the TCR combining site. In this way, the SAg isable to circumvent the normal mechanism for T-cell activation by specificpeptide/MHC complexes.