Complete modification of TCR specificity and repertoire selection does not perturb a CD8( ) T cell immunodominance hierarchy
Katherine Kedzierska, Carole Guillonneau, Stephanie Gras, Lauren A Hatton, Richard Webby, Anthony W Purcell, Jamie Rossjohn, Peter C Doherty, Stephen J Turner
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2008
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 D(b)NP(366)CD8(+) T cell response. Infection with an engineered virus (NPM6A) containing a single alanine (A) mutation at the critical p6 NP(366-374) 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 over..View full abstract
Related Projects (3)
Awarded by National Health and Medical Research Council
Awarded by National Institutes of Health
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.