Epitope-specific TCRβ repertoire diversity imparts no functional advantage on the CD8⁺ T cell response to cognate viral peptides

Abstract

TCR repertoire diversity has been convincingly shown to facilitate responsiveness of CD8⁺ T cell populations to mutant virus peptides, thereby safeguarding against viral escape. However, the impact of repertoire diversity on the functionality of the CD8⁺ T cell response to cognate peptide-MHC class I complex (pMHC) recognition remains unclear. Here, we have compared TCRβ chain repertoires of three influenza A epitope-specific CD8⁺ T cell responses in C57BL/6 (B6) mice: D^bNP_366–374, D^bPA_224–233, and a recently described epitope derived from the +1 reading frame of the influenza viral polymerase B subunit (residues 62–70) (D^bPB1-F2₆₂). Corresponding to the relative antigenicity of the respective pMHCs, and irrespective of the location of prominent residues, the D^bPA₂₂₄- and D^bPB1-F2₆₂-specific repertoires were similarly diverse, whereas the D^bNP₃₆₆ population was substantially narrower. Importantly, parallel analysis of response magnitude, cytotoxicity, TCR avidity, and cytokine production for the three epitope-specific responses revealed no obvious functional advantage conferred by increased T cell repertoire diversity. Thus, whereas a diverse repertoire may be important for recognition of epitope variants, its effect on the response to cognate pMHC recognition appears minimal.

• influenza A virus
• pMHC-TCR avidity