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Generating De Novo Antigen-specific Human T Cell Receptors by Retroviral Transduction of Centric Hemichain
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Published on: October 25, 2016

A structural basis for immunodominant human T cell receptor recognition

Guillaume B E Stewart-Jones1, Andrew J McMichael, John I Bell

  • 1Division of Structural Biology, The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, UK.

Nature Immunology
|June 11, 2003
PubMed

The anti-influenza CD8+ T cell response in HLA-A2-positive adults is almost exclusively directed at residues 58-66 of the virus matrix protein (MP(58-66)). V(beta)17V(alpha)10.2 T cell receptors (TCRs) containing a conserved arginine-serine-serine sequence in complementarity determining region 3 (CDR3) of the V(beta) segment dominate this response. To investigate the molecular basis of immunodominant selection in an outbred population, we have determined the crystal structure of V(beta)17V(alpha)10.2 in complex with MP(58-66)-HLA-A2 at a resolution of 1.4 A. We show that, whereas the TCR typically fits over an exposed side chain of the peptide, in this structure MP(58-66) exposes only main chain atoms. This distinctive orientation of V(beta)17V(alpha)10.2, which is almost orthogonal to the peptide-binding groove of HLA-A2, facilitates insertion of the conserved arginine in V(beta) CDR3 into a notch in the surface of MP(58-66)-HLA-A2. This previously unknown binding mode underlies the immunodominant T cell response.

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