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Crystal structure of the complex between human CD8αα and HLA-A2

Author

Listed:
  • George F. Gao

    (Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital)

  • José Tormo

    (‡Laboratory of Molecular Biophysics, The Rex Richards Building
    Centro de Investigacin y Desarrollo (CSIC))

  • Ulrich C. Gerth

    (Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital)

  • Jessica R. Wyer

    (Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital)

  • Andrew J. McMichael

    (Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital)

  • David I. Stuart

    (‡Laboratory of Molecular Biophysics, The Rex Richards Building
    §Oxford Centre for Molecular Sciences, New Chemistry Building)

  • John I. Bell

    (Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital)

  • E. Yvonne Jones

    (‡Laboratory of Molecular Biophysics, The Rex Richards Building
    §Oxford Centre for Molecular Sciences, New Chemistry Building)

  • Bent K. Jakobsen

    (Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital)

Abstract

The dimeric cell-surface glycoprotein CD8 is crucial to the positive selection of cytotoxic T cells in the thymus1. The homodimer CD8αα or the heterodimer αβ stabilizes the interaction of the T-cell antigen receptor (TCR) with major histocompatibility complex (MHC) class I/peptide by binding to the class I molecule2. Here we report the crystal structure at 2.7Å resolution of a complex between CD8αα and the human MHC molecule HLA-A2, which is associated with peptide. CD8αα binds one HLA-A2/peptide molecule, interfacing with the α2 and α3 domains of HLA-A2 and also contacting β2-microglobulin. A flexible loop of the α3 domain (residues 223–229) is clamped between the complementarity-determining region (CDR)-like loops of the two CD8 subunits in the classic manner of an antibody–antigen interaction, precluding the binding of a second MHC molecule. The position of the α3 domain is different from that in uncomplexed HLA-A2 (refs 3, 4), being most similar to that in the TCR/Tax/HLA-A2 complex5, but no conformational change extends to the MHC/peptide surface presented for TCR recognition. Although these shifts in α3 may provide a synergistic modulation of affinity, the binding of CD8 to MHC is clearly consistent with an avidity-based contribution from CD8 to TCR–peptide–MHC interactions.

Suggested Citation

  • George F. Gao & José Tormo & Ulrich C. Gerth & Jessica R. Wyer & Andrew J. McMichael & David I. Stuart & John I. Bell & E. Yvonne Jones & Bent K. Jakobsen, 1997. "Crystal structure of the complex between human CD8αα and HLA-A2," Nature, Nature, vol. 387(6633), pages 630-634, June.
    • Handle: RePEc:nat:nature:v:387:y:1997:i:6633:d:10.1038_42523
    DOI: 10.1038/42523
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    Cited by:

    1. Webber W P Liao & Jonathan W Arthur, 2011. "Predicting Peptide Binding Affinities to MHC Molecules Using a Modified Semi-Empirical Scoring Function," PLOS ONE, Public Library of Science, vol. 6(9), pages 1-8, September.

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