Journal article

Structural basis for enabling T-cell receptor diversity within biased virus-specific CD8 T-cell responses

EB Day, C Guillonneau, S Gras, NL La Gruta, DAA Vignali, PC Doherty, AW Purcell, J Rossjohn, SJ Turner

Proceedings of the National Academy of Sciences of the United States of America | Published : 2011

Abstract

Pathogen-specific responses are characterized by preferred profiles of peptide+class I MHC (pMHCI) glycoprotein-specific T-cell receptor (TCR) Variable (V)-region use. How TCRV-region bias impacts TCRαβ heterodimer selection and resultant diversity is unclear. The DbPA224-specific TCR repertoire in influenza A virus-infected C57BL/6J (B6) mice exhibits a preferred TCRV-region bias toward the TRBV29 gene segment and an optimal complementarity determining region (CDR3) β-length of 6 aa. Despite these restrictions, DbPA224-specific BV29+ T cells use a wide array of unique CDR3β sequences. Structural characterization of a single, TRBV29+DbPA224-specific TCRαβ-pMHCI complex demonstrated that CDR3..

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Grants

Awarded by National Institute of Allergy and Infectious Diseases


Funding Acknowledgements

We thank the staff at the General Medical Sciences and National Cancer Institute Collaborative Access Team beamline at the Argonne Photon Source for assistance. This work was supported by Australian National Health and Medical Research Council (NHMRC) program Grants 5671222 (to P.C.D., S.J.T., and J.R.), NHMRC Project Grant 508929 (to A.W.P. and S.J.T.), National Institute Health Grant AI70251 (to P.C.D.), a NHMRC Dora Lush Postgraduate Award (to E.B.D.), a Marie Curie Postdoctoral Fellowship (to C.G.), an NHMRC RD Wright Career Development Award (to N.L.L.G.), an NHMRC Senior Research Fellowship (to A.W.P.), an Australian Research Council Federation Fellowship (to J.R.), a Pfizer Senior Research Fellowship (to S.J.T.), and the Juvenile Diabetes Research Foundation International and the American Lebanese Syrian Associated Charities.