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

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 magnitude and pMHC-I avidity. For the more diverse DbPA 224+CD8+ T cells, this particular forcing led to a narrowing and higher TCRβ conservation of the dominant Vβ7, though the responses were of comparable magnitude to C57BL/6J controls. Interestingly, although both the TCRβ diversity and the cytokine profiles were reduced for the DbNP366+CD8+ and DbPA224+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" TCRαβ pairs can operate effectively when exposed in amilieu of high virus load. Thus, TCRβ diversity is important for optimal TCRαβ pairing and function when TCRα is limiting. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.