Cutting edge: culture with high doses of viral peptide induces previously unprimed CD8(+) T cells to produce cytokine.
Culturing naive T cells with 50 microM selected HIV-1 envelope peptides for 6 days in the presence of IL-2 drives the emergence of a substantial CD8(+) population that secretes IFN-gamma following short-term stimulation with 1 microM peptide. This response is H-2K(b) restricted, epitope specific, and requires the continuing presence of peptide. The same effect was found for known H-2D(b)-restricted peptides from two influenza virus proteins. The great majority of these influenza-specific CD8(+)IFN-gamma(+) T cells neither stained with the cognate tetramer nor expressed the TCR Vbeta bias that is characteristic of the CD8(+) set expanded in vivo during an infection. Thus, multipoint binding of low affinity TCRs on naive CD8(+) T cells can drive peptide-specific cytokine production. However, at least for two influenza-derived epitopes, the avidity of the TCR-MHC peptide interaction appears to be insufficient to stabilize a tetrameric complex of MHC class I glycoprotein plus peptide on the lymphocyte surface.
Riberdy
J M
JM
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. janice.riberdy@stjude.org
Zirkel
A
A
Surman
S
S
Hurwitz
J L
JL
Doherty
P C
PC
D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D000939:Epitopes / Q000008:administration & dosage; D015686:Gene Products, env / Q000008:administration & dosage / Q000276:immunology; D006183:H-2 Antigens; D015488:HIV Antigens / Q000008:administration & dosage; D015497:HIV-1 / Q000276:immunology; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D009975:Orthomyxoviridae / Q000276:immunology; D014764:Viral Proteins / Q000008:administration & dosage* / Q000276:immunology*
D016207:Cytokines; D000939:Epitopes; D015686:Gene Products, env; D006183:H-2 Antigens; D015488:HIV Antigens; D014764:Viral Proteins; D007371:Interferon-gamma