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

NL La Gruta, PG Thomas, AI Webb… - Proceedings of the …, 2008 - National Acad Sciences
Proceedings of the National Academy of Sciences, 2008National Acad Sciences
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: DbNP366–374, DbPA224–233, and a recently described …
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: DbNP366–374, DbPA224–233, and a recently described epitope derived from the +1 reading frame of the influenza viral polymerase B subunit (residues 62–70) (DbPB1-F262). Corresponding to the relative antigenicity of the respective pMHCs, and irrespective of the location of prominent residues, the DbPA224- and DbPB1-F262-specific repertoires were similarly diverse, whereas the DbNP366 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.
National Acad Sciences