Activation of murine epidermal V gamma 5/V delta 1-TCR+ T cells lines by Glu-Tyr polypeptides

Abstract

The physiologic role of gamma delta -T-cell-receptor-bearing cells and the T cell receptor ligands that they recognize is still poorly understood. Previous studies have suggested that one possible antigen for gamma delta -TCR+ cells is the random copolymer poly-glutamic acid-tyrosine (poly-Glu-Tyr), because poly-Glu-Tyr-reactive gamma delta -TCR hybridoma cells were produced from poly-Glu-Tyr-immunized mice, We have found, however that clonal V gamma5/V delta1-TCR+ epidermal T cell lines from nonimmune mice also respond to poly-Glu-Tyr by producing cytokines, Other amino acid homopolymers, copolymers, and tripolymers were not stimulatory for the V gamma5/V delta1-TCR+ epidermal T cells, except for poly-glutamic acid-alanine-tyro sine (poly-Glu-Ala-Tyr). Of the poly-Glu-Tyr and poly-Glu-Ala-Tyr polymers, only those that contained Glu and Tyr in an equimolar ratio were stimulatory. The cytokine interleukin-2 was strictly required for the responses to poly-Glu-Ala-Tyr, whereas the responses to poly-Glu-Tyr were merely enhanced with interleukin-2. The response to poly-Glu-Tyr was also enhanced by crosslinking CD28 molecules with plate-bound anti-CD28 crosslinking antibody. This finding suggests that the poly-Glu-Tyr response has a partial dependence on CD28-mediated costimulation, a characteristic of TCR-dependent responses. Consistent with this observation, V gamma5/V delta1-TCR-loss variants of the epidermal T cell line could no longer respond to poly-Glu-Tyr. The unpredicted responses of epidermal gamma delta -TCR+ T cells to poly-Glu-Tyr and poly-Glu-Ala-Tyr demonstrate that the functions of these cells potentially can be triggered by peptidic ligands, probably through a TCR-mediated process.