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

Turner, S. J. et al. (2005) Lack of prominent peptide–major histocompatibility complex features limits repertoire diversity in virus-specific CD8+ T cell populations. Nature Immunology, 6(4), pp. 382-389. (doi: 10.1038/ni1175) (PMID:15735650)

Abstract

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-2Db. Here we show the H-2Db−NP366 complex with a 'featureless' structure selected a limited TCR repertoire characterized by 'public' TCR usage. In contrast, the prominent H-2Db−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-2Db−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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Walden, Professor Helen
• Authors: Turner, S. J., Kedzierska, K., Komodromou, H., La Gruta, N. L., Dunstone, M. A., Webb, A. I., Webby, R., Walden, H., Xie, W., McCluskey, J., Purcell, A. W., Rossjohn, J., and Doherty, P. C.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Nature Immunology
• Publisher: Nature Publishing Group
• ISSN: 1529-2908
• ISSN (Online): 1529-2916
• Published Online: 27 February 2005