Complete modification of TCR specificity and repertoire selection does not perturb a CD8 T cell immunodominance hierarchy

K Kedzierska; C Guillonneau; S Gras; LA Hatton; R Webby; AW Purcell; J Rossjohn; PC Doherty; SJ Turner

Journal article

Complete modification of TCR specificity and repertoire selection does not perturb a CD8 T cell immunodominance hierarchy

K Kedzierska, C Guillonneau, S Gras, LA Hatton, R Webby, AW Purcell, J Rossjohn, PC Doherty, SJ Turner

Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2008

DOI: 10.1073/pnas.0810274105

Abstract

Understanding T cell immunodominance hierarchies is fundamental to the development of cellular-based vaccines and immunotherapy. A combination of influenza virus infection in C57BL/6J mice and reverse genetics is used here to dissect the role of T cell antigen receptor (TCR) repertoire in the immunodominant DbNP366CD8+ T cell response. Infection with an engineered virus (NPM6A) containing a single alanine (A) mutation at the critical p6 NP366-374 residue induced a noncross-reactive CD8+ T cell response characterized by a novel, narrower TCR repertoire per individual mouse that was nonetheless equivalent in magnitude to that generated after WT virus challenge. Although of lower overall avidit..

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University of Melbourne Researchers

Katherine Kedzierska Author

Jamie Rossjohn Author

Peter Doherty Author

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Grants

Awarded by National Health and Medical Research Council

Awarded by National Institutes of Health

Funding Acknowledgements

We thank Drs. N. La Gruta and J. Stambas for review of the manuscript, Ken Field for sorting, and Dina Stockwell for technical assistance. This work was funded by National Health and Medical Research Council Project Grants AI454595 (to P. C. D.), AI508929 (to A. W. P. and S. J. T.) and AI454312 (to K. K.), a University of Melbourne Early Career Researcher Grant (to K. K.), and National Institutes of Health Grant AI170251. K. K. is a National Health and Medical Research Council R. D. Wright Fellow. S. J. T. is a Pfizer Senior Research Fellow. C. G. is a Marie Curie International Fellow (040840). J. R. is an Australian Research Council Federation Fellow. A. W. P. is a National Health and Medical Research Council Senior Research Fellow.