Unique antigen recognition by a herpesvirus-specific TCR-γδ cell

TCR-γδ cells, a T cell subset present in the epithelial and lymphoid tissues, have been implicated in viral and bacterial infections. We have identified a TCR-γδ clone (TgI4.4) that, unlike TCR-αβ cells, recognizes a herpes simplex virus type 1 transmembrane glycoprotein, gl, in an MHC class I- and class II-independent fashion. The TCR of TgI4.4 is composed of rearranged Vδ8 (a Vα2 family member) and Vγ1.2 variable genes, a heterodimeric pair not previously described. Furthermore, anti-Vα2 mAbs are sufficient to block recognition of the gl ligand. Strikingly, anti-gI Abs also are capable of blocking recognition, a phenomena that is very rare in TCR-αβ Ag recognition. Therefore, to dissect the mechanism involved in this unique form of Ag recognition, we constructed a mutant of gl, glt, that lacks cell surface expression upon transfection into APCs. This form of gl was not sufficient for Ag presentation. In contrast, wild-type gl expressed in the Ag-processing mutant cell, RMA-S, is recognized by TgI4.4, suggesting that gl presentation occurs independently of classical Ag-processing pathways. In fact, through the use of a soluble recombinant gI molecule, gI-Ig, we show that TgI4.4 can recognize whole, unprocessed gI protein in the absence of any APCs. These results suggest that there exist alternate and novel forms of TCR Ag recognition, and that the TCR-γδ clone, TgI4.4, may represent a novel T cell subset that, during pathogenic challenge, may respond directly to Ags on the surfaces of bacteria and viruses.