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The basis for limited specificity and MHC restriction in a T cell receptor interface

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  • Kurt H. Piepenbrink

    (251 Nieuwland Science Hall, University of Notre Dame
    Present address: Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Room N557, Baltimore, Maryland 21201, USA)

  • Sydney J. Blevins

    (251 Nieuwland Science Hall, University of Notre Dame)

  • Daniel R. Scott

    (251 Nieuwland Science Hall, University of Notre Dame)

  • Brian M. Baker

    (251 Nieuwland Science Hall, University of Notre Dame
    The Harper Cancer Research Institute, 251 Nieuwland Science Hall, University of Notre Dame)

Abstract

αβ T cell receptors (TCRs) recognize peptides presented by major histocompatibility complex (MHC) proteins using multiple complementarity-determining region (CDR) loops. TCRs display an array of poorly understood recognition properties, including specificity, crossreactivity and MHC restriction. Here we report a comprehensive thermodynamic deconstruction of the interaction between the A6 TCR and the Tax peptide presented by the class I MHC HLA-A*0201, uncovering the physical basis for the receptor’s recognition properties. Broadly, our findings are in conflict with widely held generalities regarding TCR recognition, such as the relative contributions of central and peripheral peptide residues and the roles of the hypervariable and germline CDR loops in engaging peptide and MHC. Instead, we find that the recognition properties of the receptor emerge from the need to engage the composite peptide/MHC surface, with the receptor utilizing its CDR loops in a cooperative fashion such that specificity, crossreactivity and MHC restriction are inextricably linked.

Suggested Citation

  • Kurt H. Piepenbrink & Sydney J. Blevins & Daniel R. Scott & Brian M. Baker, 2013. "The basis for limited specificity and MHC restriction in a T cell receptor interface," Nature Communications, Nature, vol. 4(1), pages 1-9, October.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2948
    DOI: 10.1038/ncomms2948
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