Cutting edge: Culture with high doses of viral peptide induces previously unprimed CD8(+) T cells to produce cytokine

Culturing naive T cells with 50 muM selected HIV-1 envelope peptides for 6 days in the presence of IL-2 drives the emergence of a substantial CD8(+) p opulation that secretes IFN-gamma following short-term stimulation with 1 m uM peptide. This response is H-2K(b) restricted, epitope specific, and requ ires the continuing presence of peptide. The same effect was found for know n H-2D(b)-restricted peptides from two influenza virus proteins. The great majority of these influenza-specific CD8(+)IFN-gamma (+) T cells neither st ained with the cognate tetramer nor expressed the TCR V beta bias that is c haracteristic of the CD8+ set expanded in vivo during an infection. Thus, m ultipoint binding of low affinity TCRs on naive CD8(+) T cells can drive pe ptide-specific cytokine production. However, at least for two influenza-der ived epitopes, the avidity of the TCRMHC peptide interaction appears to be insufficient to stabilize a tetrameric complex of MHC class I glycoprotein plus peptide on the lymphocyte surface.