Nature Immunology6, 382 - 389 (2005)
Published online: 27 February 2005; | doi:10.1038/ni1175
Lack of prominent peptide−major histocompatibility complex features limits repertoire diversity in virus-specific CD8+ T cell populations
Stephen J Turner1, Katherine Kedzierska1, Helen Komodromou1, Nicole L La Gruta1, Michelle A Dunstone2, Andrew I Webb2, Richard Webby3, Helen Walden3, Wiedong Xie3, James McCluskey1, Anthony W Purcell1, Jamie Rossjohn2
& Peter C Doherty1, 3
1
Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia.
2
The Protein Crystallography Unit, Monash Centre for Synchrotron Science, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
3
Departments of Infectious Diseases, Structural Biology, and Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, 38105 USA.
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.
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