Journal article

Fixing an irrelevant TCR alpha chain reveals the importance of TCR beta diversity for optimal TCR alpha beta pairing and function of virus-specific CD8( ) T cells

Sophie A Valkenburg, E Bridie Day, Natasha G Swan, Hayley A Croom, Francis R Carbone, Peter C Doherty, Stephen J Turner, Katherine Kedzierska

EUROPEAN JOURNAL OF IMMUNOLOGY | WILEY | Published : 2010

Abstract

TCR repertoire diversity can influence the efficacy of CD8(+) T-cell populations, with greater breadth eliciting better protection. We analyzed TCR beta diversity and functional capacity for influenza-specific CD8(+) T cells expressing a single TCR alpha chain. Mice (A7) transgenic for the H2K(b)OVA(257-264)-specific V alpha 2.7 TCR were challenged with influenza to determine how fixing this "irrelevant" TCR alpha affects the "public" and restricted D(b)NP(366) (+)CD8(+) versus the "private" and diverse D(b)PA(224) (+)CD8(+) responses. Though both D(b)NP(366) (+)CD8(+) and D(b)PA(224) (+)CD8(+) sets are generated in virus-primed A7 mice, the constrained D(b)NP(366) (+)CD8(+) population lacke..

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Grants

Awarded by Australian National Health and Medical Research Council (NHMRC)


Awarded by NIH


Funding Acknowledgements

The authors thank Dina Stockwell for technical assistance, Ken Field for FACS sorting and Serrin Rowarth for providing the A7 mice. This work was supported by Australian National Health and Medical Research Council (NHMRC) Project Grants to KK (AI454312) and PCD (AI454595), an NHMRC Program Grant # 567122 (to PCD and SJT), and NIH grant AI170251. K. K. is an NHMRC RD Wright Fellow and S. J. T. is a Pfizer Senior Research Fellow. S. A. V. is a recipient of the Australian Postgraduate Award and E. B. D. of the NHMRC Postgraduate Biomedical Scholarship.