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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
Summary
The influenza matrix protein (MP(58-66)) triggers a CD8+ T cell response in HLA-A2 adults. A unique T cell receptor (TCR) binding mode, exposing main chain atoms, drives this immunodominance.
Area of Science:
- Immunology
- Structural Biology
- Virology
Background:
- The anti-influenza CD8+ T cell response in HLA-A2 adults targets the virus matrix protein (MP(58-66)).
- This response is dominated by V(beta)17V(alpha)10.2 T cell receptors (TCRs) with a specific CDR3 motif.
Purpose of the Study:
- To investigate the molecular basis of immunodominant T cell selection in an outbred population.
- To elucidate the structural interactions between the dominant TCR and its cognate peptide-MHC complex.
Main Methods:
- Determined the crystal structure of the V(beta)17V(alpha)10.2 TCR in complex with MP(58-66)-HLA-A2 at 1.4 A resolution.
Main Results:
- The MP(58-66) peptide presented by HLA-A2 exposes primarily main chain atoms to the TCR, unlike typical peptide side chain presentation.
- The V(beta)17V(alpha)10.2 TCR adopts an almost orthogonal orientation to the peptide-binding groove.
- A conserved arginine in the TCR's V(beta) CDR3 inserts into a specific notch on the MP(58-66)-HLA-A2 complex.
Conclusions:
- A previously unrecognized TCR-peptide-MHC binding mode, involving main chain atom exposure and specific arginine insertion, underlies the immunodominant anti-influenza T cell response.