Influenza epitope-specific CD8+ T cell avidity, but not cytokine polyfunctionality, can be determined by TCRβ clonotype.
Cytokine polyfunctionality has recently emerged as a correlate of effective CTL immunity to viruses and tumors. Although the determinants of polyfunctionality remain unclear, there are published instances of a link between the production of multiple effector molecules and the peptide plus MHC class I molecule avidity of T cell populations. Influenza A virus infection of C57BL/6J mice induces CTL populations specific for multiple viral epitopes, each with varying proportions of monofunctional (IFN-γ(+) only) or polyfunctional (IFN-γ(+)TNF-α(+)IL-2(+)) CTLs. In this study, we probe the link between TCR avidity and polyfunctionality for two dominant influenza epitopes (D(b)NP(366) and D(b)PA(224)) by sequencing the TCR CDR3β regions of influenza-specific IFN-γ(+) versus IFN-γ(+)IL-2(+) cells, or total tetramer(+) versus high-avidity CTLs (as defined by the peptide plus MHC class I molecule-TCR dissociation rate). Preferential selection for particular clonotypes was evident for the high-avidity D(b)PA(224)-specific set but not for any of the other subsets examined. These data suggest that factors other than TCRβ sequence influence cytokine profiles and demonstrate no link between differential avidity and polyfunctionality.
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
Jessica M
JM
Moffat
Andreas
A
Handel
Peter C
PC
Doherty
Stephen J
SJ
Turner
Paul G
PG
Thomas
Nicole L
NL
La Gruta
D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D016056:Immunodominant Epitopes / Q000276:immunology / Q000378:metabolism; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D016056:Immunodominant Epitopes; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta