Fixing an irrelevant TCRα chain reveals the importance of TCRβ diversity for optimal TCRαβ pairing and function of virus-specific CD8 T cells

SA Valkenburg; EB Day; NG Swan; HA Croom; FR Carbone; PC Doherty; SJ Turner; K Kedzierska

Journal article

Fixing an irrelevant TCRα chain reveals the importance of TCRβ diversity for optimal TCRαβ pairing and function of virus-specific CD8 T cells

SA Valkenburg, EB Day, NG Swan, HA Croom, FR Carbone, PC Doherty, SJ Turner, K Kedzierska

European Journal of Immunology | WILEY | Published : 2010

DOI: 10.1002/eji.201040473

Abstract

TCR repertoire diversity can influence the efficacy of CD8+ T-cell populations, with greater breadth eliciting better protection. We analyzed TCRβ diversity and functional capacity for influenza-specific CD8+ T cells expressing a single TCRα chain. Mice (A7) transgenic for the H2KbOVA257-264-specific Vα2.7 TCR were challenged with influenza to determine how fixing this "irrelevant" TCRα affects the "public" and restricted DbNP366+CD8+ versus the "private" and diverse DbPA224 +CD8+ responses. Though both DbNP 366+CD8+ and DbPA224 +CD8+ sets are generated in virus-primed A7 mice, the constrained DbNP366+CD8+ population lacked the characteristic, public TCRVβ8.3, and consequently was reduced in..

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University of Melbourne Researchers

Bridie Clemens Author

Francis Carbone Author

Peter Doherty Author

Katherine Kedzierska Author

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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.