Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 40, Issue 9, Pages 2470-2481Publisher
WILEY
DOI: 10.1002/eji.201040473
Keywords
CD8(+) T cells; Influenza; TCR repertoire; Viral infection
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Funding
- Australian National Health and Medical Research Council (NHMRC) [AI454312, AI454595, 567122]
- NIH [AI170251]
- Australian Postgraduate Award
- NHMRC Postgraduate Biomedical Scholarship
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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 TCRa 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 lacked the characteristic, public TCRV beta 8.3, and consequently was reduced in magnitude and pMHC-I avidity. For the more diverse D(b)PA(224)(+)CD8(+) T cells, this particular forcing led to a narrowing and higher TCRb conservation of the dominant V beta 7, though the responses were of comparable magnitude to C57BL/6J controls. Interestingly, although both the TCRb diversity and the cytokine profiles were reduced for the D(b)NP(366)(+)CD8(+) and D(b)PA(224)(+)CD8(+) sets in spleen, the latter measure of polyfunctionality was comparable for T cells recovered from the infected lungs of A7 and control mice. Even sub-optimal TCR alpha beta pairs can operate effectively when exposed in a milieu of high virus load. Thus, TCR beta diversity is important for optimal TCR alpha beta pairing and function when TCR alpha is limiting.
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