Lack of prominent peptide-major histocompatibility complex features limits repertoire diversity in virus-specific CD8+ T cell populations

Nat Immunol. 2005 Apr;6(4):382-9. doi: 10.1038/ni1175. Epub 2005 Feb 27.


Using both 'reverse genetics' and structural analysis, we have examined the in vivo relationship between antigenicity and T cell receptor (TCR) repertoire diversity. Influenza A virus infection of C57BL/6 mice induces profoundly different TCR repertoires specific for the nucleoprotein peptide of amino acids 366-374 (NP366) and the acid polymerase peptide of amino acids 224-233 (PA224) presented by H-2D(b). Here we show the H-2D(b)-NP366 complex with a 'featureless' structure selected a limited TCR repertoire characterized by 'public' TCR usage. In contrast, the prominent H-2D(b)-PA224 complex selected diverse, individually 'private' TCR repertoires. Substitution of the arginine at position 7 of PA224 with an alanine reduced the accessible side chains of the epitope. Infection with an engineered virus containing a mutation at the site encoding the exposed arginine at position 7 of PA224 selected a restricted TCR repertoire similar in diversity to that of the H-2D(b)-NP366-specific response. Thus, the lack of prominent features in an antigenic complex of peptide and major histocompatibility complex class I is associated with a diminished spectrum of TCR usage.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigenic Variation / immunology
  • Antigens, Viral / chemistry
  • Antigens, Viral / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Crystallography, X-Ray
  • Epitopes, T-Lymphocyte / immunology*
  • Histocompatibility Antigens / immunology
  • Influenza A virus / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Models, Molecular
  • Molecular Sequence Data
  • Orthomyxoviridae Infections / immunology
  • Point Mutation
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes, Cytotoxic / immunology


  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens
  • Receptors, Antigen, T-Cell

Associated data

  • PDB/1YN6
  • PDB/1YN7