Epitope-specific TCRbeta repertoire diversity imparts no functional advantage on the CD8+ T cell response to cognate viral peptides.
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.
La Gruta
Nicole L
NL
Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Victoria, Australia.
Thomas
Paul G
PG
Webb
Andrew I
AI
Dunstone
Michelle A
MA
Cukalac
Tania
T
Doherty
Peter C
PC
Purcell
Anthony W
AW
Rossjohn
Jamie
J
Turner
Stephen J
SJ
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*
D000939:Epitopes; D007376:Interleukin-2; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins