Abstract
SUPERANTIGENS (SAgs) are viral or bacterial proteins that act as potent T-cell stimulants and have been implicated in a number of human diseases, including toxic shock syndrome1,2, diabetes mellitus3 and multiple sclerosis4. The interaction of SAgs with the T-cell receptor (TCR) and major histocompatibility complex (MHC) proteins results in the stimulation of a disproportionately large fraction of the T-cell population2. We report here the crystal structures of the β-chain of a TCR complexed with the Staphylococcus aureus enterotoxins C2 and C3 (SEC2, SEC3). These enterotoxins, which cause both toxic shock and food poisoning, bind in an identical way to the TCR β-chain. The complementarity-determining region 2 (CDR2) of the β-chain and, to lesser extents, CDR1 and hypervariable region 4 (HV4), bind in a cleft between the two domains of the SAgs. Thus, there is considerable overlap between the SAg-binding site and the peptide/MHC-binding sites of the TCR. A model of a TCR–SAg–MHC complex constructed from the crystal structures of (1) the β-chain–SEC3 complex, (2) a complex between staphylococcal enterotoxin B (SEB) and an MHC molecule5, and (3) a TCR Vα domain6, 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 is able to circumvent the normal mechanism for T-cell activation by specific peptide/MHC complexes.
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Fields, B., Malchiodi, E., Li, H. et al. Crystal structure of a T-cell receptor β-chain complexed with a superantigen. Nature 384, 188–192 (1996). https://doi.org/10.1038/384188a0
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DOI: https://doi.org/10.1038/384188a0
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