UNIQUE ANTIGEN RECOGNITION BY A HERPESVIRUS-SPECIFIC TCR-GAMMA-DELTA CELL

TCR-gamma delta cells, a T cell subset present in the epithelial and l ymphoid tissues, have been implicated in viral and bacterial infection s. We have identified a TCR-gamma delta clone (TgI4.4) that, unlike TC R-alpha beta cells, recognizes a herpes simplex virus type 1 transmemb rane glycoprotein, gl, in an MHC class I- and class II-independent fas hion. The TCR of TgI4.4 is composed of rearranged V delta 8 (a V alpha 2 family member) and V gamma 1.2 variable genes, a heterodimeric pair not previously described. Furthermore, anti-V alpha 2 mAbs are suffic ient to block recognition of the gl ligand. Strikingly, anti-gl Abs al so are capable of blocking recognition, a phenomena that is very rare in TCR-alpha beta Ag recognition. Therefore, to dissect the mechanism involved in this unique form of Ag recognition, we constructed a mutan t of gl, glt, that lacks cell surface expression upon transfection int o APCs. This form of gl was not sufficient for Ag presentation. In con trast, wild-type gl expressed in the Ag-processing mutant cell, RMA-S, is recognized by TgI4.4, suggesting that gl presentation occurs indep endently of classical Ag-processing pathways. In fact, through the use of a soluble recombinant gl molecule, gl-lg, we show that TgI4.4 can recognize whole, unprocessed gl protein in the absence of any APCs. Th ese results suggest that there exist alternate and novel forms of TCR Ag recognition, and that the TCR-gamma delta clone, TgI4.4, may repres ent a novel T cell subset that, during pathogenic challenge, may respo nd directly to Ags on the surfaces of bacteria and viruses,