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

Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2034-9. doi: 10.1073/pnas.0711682102. Epub 2008 Jan 31.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Epitopes / immunology*
  • Female
  • Interleukin-2 / biosynthesis
  • Mice
  • Models, Molecular
  • Peptides / immunology*
  • Protein Conformation
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Viral Proteins / chemistry
  • Viral Proteins / immunology*

Substances

  • Epitopes
  • Interleukin-2
  • Peptides
  • Receptors, Antigen, T-Cell, alpha-beta
  • Tumor Necrosis Factor-alpha
  • Viral Proteins