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Epitope-specific TCRbeta 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 TCRbeta chain repertoires of three influenza A epitope-specific CD8+ T cell responses in C57BL/6 (B6) mice: D(b)NP(366-374), D(b)PA(224-233), and a recently described epitope derived from the +1 reading frame of the influenza viral polymerase B subunit (residues 62-70) (D(b)PB1-F2(62)). Corresponding to the relative antigenicity of the respective pMHCs, and irrespective of the location of prominent residues, the D(b)PA(224)- and D(b)PB1-F2(62)-specific repertoires were similarly diverse, whereas the D(b)NP(366) 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.

SUBMITTER: La Gruta NL 

PROVIDER: S-EPMC2538877 | biostudies-other | 2008 Feb

REPOSITORIES: biostudies-other

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

La Gruta Nicole L NL   Thomas Paul G PG   Webb Andrew I AI   Dunstone Michelle A MA   Cukalac Tania T   Doherty Peter C PC   Purcell Anthony W AW   Rossjohn Jamie J   Turner Stephen J SJ  

Proceedings of the National Academy of Sciences of the United States of America 20080131 6


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 TCRbeta chain repertoires of three influenza A epitope-specific CD8+ T cell responses in C57BL/6 (B6) mice: D(b)NP(366-374), D(b)PA  ...[more]

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