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Cutting Edge: Culture with High Doses of Viral Peptide Induces Previously Unprimed CD8⁺ T Cells to Produce Cytokine¹

Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN, 38105

Culturing naive T cells with 50 µM 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- following short-term stimulation with 1 µM 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-⁺ T cells neither stained with the cognate tetramer nor expressed the TCR V 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.

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