title: Epitope-specific TCRbeta repertoire diversity imparts no functional advantage on the CD8+ T cell response to cognate viral peptides.
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.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Victoria, Australia.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: La Gruta
authors.forename: Paul G
authors.initials: PG
authors.lastname: Thomas
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Webb
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Dunstone
authors.forename: Tania
authors.initials: T
authors.lastname: Cukalac
authors.forename: Peter C
authors.initials: PC
authors.lastname: Doherty
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Purcell
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Turner
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D008958:Models, Molecular; D010455:Peptides / Q000276:immunology*; D011487:Protein Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology*
chemical_list: D000939:Epitopes; D007376:Interleukin-2; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins