Crystal structure of a complete ternary complex of TCR, superantigen and peptide-MHC

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Abstract

'Superantigens' (SAgs) trigger the massive activation of T cells by simultaneous interactions with MHC and TCR receptors, leading to human diseases. Here we present the first crystal structure, at 2.5-Å resolution, of a complete ternary complex between a SAg and its two receptors, HLA-DR1/HA and TCR. The most striking finding is that the SAg Mycoplasma arthritidis mitogen, unlike others, has direct contacts not only with TCR Vβ but with TCR Vα.

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Figure 1: Crystal structure of scTCR–MAM–HLA-DR1/HA ternary complex.
Figure 2: Conformational changes in MAM and TCR upon complex formation.

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Acknowledgements

This research was supported by grants AI50628 (to H.L.) and AI064611 (to D.M.K.) from the US National Institutes of Health. W.M. is supported by grants from the Arthritis Society of Canada, the Canadian Arthritis Network and the Canadian Institutes of Health Research. We thank A. Verschoor for critical reading of the manuscript, L.J. Stern (University of Massachusetts Medical School) for the gift of HLA-DR1 expression plasmids, and core facilities at the Wadsworth Center, including the Peptide Synthesis, Molecular Genetics and Macromolecular Crystallography cores, for synthesis of the HA peptide, DNA sequencing and crystal evaluation. Data for this study were collected at beamline X4A of the National Synchrotron Light Source, which is supported by the US Department of Energy, by grants from the US National Institutes of Health and by the New York Structural Biology Center.

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Correspondence to Hongmin Li.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Details of the MAM-scTCR interface. (PDF 707 kb)

Supplementary Table 1

Data collection and refinement statistics. (PDF 18 kb)

Supplementary Table 2

Interactions between TCR and MAM. (PDF 17 kb)

Supplementary Methods (PDF 65 kb)

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Wang, L., Zhao, Y., Li, Z. et al. Crystal structure of a complete ternary complex of TCR, superantigen and peptide-MHC. Nat Struct Mol Biol 14, 169–171 (2007) doi:10.1038/nsmb1193

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