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

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 H2K^bOVA_257–264‐specific Vα2.7 TCR were challenged with influenza to determine how fixing this “irrelevant” TCRα affects the “public” and restricted D^bNP ${}_{\text{366}}^{\text{+}}$CD8⁺ versus the “private” and diverse D^bPA ${}_{\text{224}}^{\text{+}}$CD8⁺ responses. Though both D^bNP ${}_{\text{366}}^{\text{+}}$CD8⁺ and D^bPA ${}_{\text{224}}^{\text{+}}$CD8⁺ sets are generated in virus‐primed A7 mice, the constrained D^bNP ${}_{\text{366}}^{\text{+}}$CD8⁺ population lacked the characteristic, public TCRVβ8.3, and consequently was reduced in magnitude and pMHC‐I avidity. For the more diverse D^bPA ${}_{\text{224}}^{\text{+}}$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 D^bNP ${}_{\text{366}}^{\text{+}}$CD8⁺ and D^bPA ${}_{\text{224}}^{\text{+}}$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 a milieu of high virus load. Thus, TCRβ diversity is important for optimal TCRαβ pairing and function when TCRα is limiting.