Molecular basis for universal HLA-A∗0201-restricted CD8 T-cell immunity against influenza viruses

SA Valkenburg; TM Josephs; EB Clemens; EJ Grant; THO Nguyen; GC Wang; DA Price; A Miller; SYC Tong; PG Thomas; PC Doherty; J Rossjohn; S Gras; K Kedzierska

Journal article

Molecular basis for universal HLA-A∗0201-restricted CD8 T-cell immunity against influenza viruses

SA Valkenburg, TM Josephs, EB Clemens, EJ Grant, THO Nguyen, GC Wang, DA Price, A Miller, SYC Tong, PG Thomas, PC Doherty, J Rossjohn, S Gras, K Kedzierska

Proceedings of the National Academy of Sciences of the United States of America | Published : 2016

DOI: 10.1073/pnas.1603106113

Abstract

Memory CD8+ T lymphocytes (CTLs) specific for antigenic peptides derived from internal viral proteins confer broad protection against distinct strains of influenza A virus (IAV). However, immune efficacy can be undermined by the emergence of escape mutants. To determine how T-cell receptor (TCR) composition relates to IAV epitope variability, we used ex vivo peptide-HLA tetramer enrichment and single-cell multiplex analysis to compare TCRs targeted to the largely conserved HLA-A∗0201-M158 and the hypervariable HLA-B∗3501-NP418 antigens. The TCRαβs for HLA-B∗3501-NP418+ CTLs varied among individuals and across IAV strains, indicating that a range of mutated peptides will prime different NP418..

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University of Melbourne Researchers

Sophie Valkenburg Author

Bridie Clemens Author

Oanh Nguyen Author

Peter Doherty Author

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Grants

Awarded by National Institute of Allergy and Infectious Diseases

Funding Acknowledgements

We thank Nicola Bird for technical assistance and Natalie Saunders for sorting. The C1R-B<SUP>star</SUP>3501 plasmid was provided by Dr. David Cole (Cardiff University). HLA-A2.1 transgenic HHD mice were developed and provided by Dr. Francois Lemonnier (Pasteur Institute). This work was supported by National Health and Medical Research Council (NHMRC) Project Grant 1042662 (to A.M., S.Y.C.T., and K.K.) and NHMRC Program Grant 567122 (to P.C.D. and K.K.). S.A.V. is an NHMRC Early Career Research Fellow, E.B.C. is an NHMRC Peter Doherty Fellow, D.A.P. is a Wellcome Trust Senior Investigator, S.Y.C.T. and K.K. are NHMRC Career Development Fellows, J.R. is an NHMRC Australia Fellow (AF50), and S.G. is an Australian Research Council Future Fellow (FT120100416). E.J.G. is a recipient of an NHMRC Aboriginal and Torres Strait Islander Health Research Scholarship.