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Crystal structure of a T cell receptor bound to an allogeneic MHC molecule

Nature Immunology volume 1, pages 291–297 (2000)Cite this article

An Erratum to this article was published on 01 November 2000

Abstract

Many T cell receptors (TCRs) that are selected to respond to foreign peptide antigens bound to self major histocompatibility complex (MHC) molecules are also reactive with allelic variants of self-MHC molecules. This property, termed alloreactivity, causes graft rejection and graft-versus-host disease. The structural features of alloreactivity have yet to be defined. We now present a basis for this cross-reactivity, elucidated by the crystal structure of a complex involving the BM3.3 TCR and a naturally processed octapeptide bound to the H-2Kb allogeneic MHC class I molecule. A distinguishing feature of this complex is that the eleven-residue-long complementarity-determining region 3 (CDR3) found in the BM3.3 TCRα chain folds away from the peptide binding groove and makes no contact with the bound peptide, the latter being exclusively contacted by the BM3.3 CDR3β. Our results formally establish that peptide-specific, alloreactive TCRs interact with allo-MHC in a register similar to the one they use to contact self-MHC molecules.

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Figure 1: The affinity of BM3.3 scFv TCR binding to the pBM1–H-2Kb alloantigen.
Figure 2: Structure of the BM3.3–pBM1–H-2Kb complex.
Figure 3: Peptide-TCR interactions occurring at the interface of four TCR-pMHC class I complexes.
Figure 4: Identification of pBMI amino acids critical for BM3.3 transgenic TCR recognition.
Figure 5: Docking of TCRs to pMHC class I ligands.

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Acknowledgements

We thank S. Nathenson for the pET-3a Kb and pET-3a B2m plasmids; P. A. van der Merwe for advice on surface plasmon resonance; P. Fourquet for peptide synthesis; J.Bonicel for mass spectrometry analysis; L. Leserman, J. Howard and P. Golstein for comments on the manuscript, W. Burmeister for help with synchrotron data collection at ESFR ID4eh3 beamline and N. Guglietta for editing the manuscript. T. M. was supported by a fellowship from ARC. This work was supported by institutional grants from CNRS, CEA, INSERM and a specific grant from ARC.

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Authors and Affiliations

  1. Laboratoire de Cristallographie et Cristallogénèse des Protéines, Institut de Biologie Structurale J.-P. Ebel, CEA-CNRS-UJF , 41, rue Jules Horowitz, Grenoble, Cedex 1, F-38027, France

    Jean-Baptiste Reiser, Claudine Darnault, Juan Carlos Fontecilla-Camps & Dominique Housset

  2. Centre d'Immunologie INSERM-CNRS de Marseille-Luminy , Case 906, Marseille, Cedex 9, F-13288, France

    Annick Guimezanes, Claude Grégoire, Thomas Mosser, Anne-Marie Schmitt-Verhulst, Bernard Malissen & Gilbert Mazza

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  1. Jean-Baptiste Reiser
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Correspondence to Dominique Housset.

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Reiser, JB., Darnault, C., Guimezanes, A. et al. Crystal structure of a T cell receptor bound to an allogeneic MHC molecule . Nat Immunol 1, 291–297 (2000). https://doi.org/10.1038/79728

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