Influenza epitope-specific CD8+ T cell avidity, but not cytokine polyfunctionality, can be determined by TCRβ clonotype.

Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE

Publication: Bethesda, MD : American Association of Immunologists
Original Publication: Baltimore : Williams & Wilkins, c1950-

Cytokines/*physiology ; Epitopes, T-Lymphocyte/*immunology ; Influenza A Virus, H1N1 Subtype/*immunology ; Receptors, Antigen, T-Cell, alpha-beta/*metabolism ; T-Lymphocytes, Cytotoxic/*cytology ; T-Lymphocytes, Cytotoxic/*immunology; Animals ; Cell Adhesion/immunology ; Clone Cells ; Cytokines/biosynthesis ; Epitopes, T-Lymphocyte/metabolism ; Female ; H-2 Antigens/immunology ; H-2 Antigens/metabolism ; Histocompatibility Antigen H-2D ; Immunodominant Epitopes/immunology ; Immunodominant Epitopes/metabolism ; Interleukin-2/biosynthesis ; Mice ; Mice, Inbred C57BL ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/metabolism ; Receptors, Antigen, T-Cell, alpha-beta/biosynthesis ; Receptors, Antigen, T-Cell, alpha-beta/physiology ; T-Lymphocytes, Cytotoxic/metabolism

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.

AI072193 United States AI NIAID NIH HHS; K25 AI072193 United States AI NIAID NIH HHS; AI077714 United States AI NIAID NIH HHS; AI70251 United States AI NIAID NIH HHS; AI065097 United States AI NIAID NIH HHS

0 (Cytokines)
0 (Epitopes, T-Lymphocyte)
0 (H-2 Antigens)
0 (Histocompatibility Antigen H-2D)
0 (Immunodominant Epitopes)
0 (Interleukin-2)
0 (Receptors, Antigen, T-Cell, alpha-beta)

Date Created: 20101103 Date Completed: 20110110 Latest Revision: 20211020

20240829

10.4049/jimmunol.1002025

21041725