title: Lack of prominent peptide-major histocompatibility complex features limits repertoire diversity in virus-specific CD8+ T cell populations.
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-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.
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Turner
authors.forename: Katherine
authors.initials: K
authors.lastname: Kedzierska
authors.forename: Helen
authors.initials: H
authors.lastname: Komodromou
authors.forename: Nicole L
authors.initials: NL
authors.lastname: La Gruta
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Dunstone
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Webb
authors.forename: Richard
authors.initials: R
authors.lastname: Webby
authors.forename: Helen
authors.initials: H
authors.lastname: Walden
authors.forename: Wiedong
authors.initials: W
authors.lastname: Xie
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Purcell
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: Peter C
authors.initials: PC
authors.lastname: Doherty
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000940:Antigenic Variation / Q000276:immunology; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018360:Crystallography, X-Ray; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000276:immunology; D017354:Point Mutation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D006649:Histocompatibility Antigens; D011948:Receptors, Antigen, T-Cell