HLA class I-restricted recognition of an HIV-derived epitope peptide by a human T cell receptor α chain having a Vδ1 variable segment

Abstract

A subset of human peripheral αβ T cells have been shown to express TCR α chains containing Vδ1 segments, although what antigens the Vδ1+ αβ T cells recognize via these TCR is not known yet. We eventually established a human CD8 T cell clone that expressed αβ TCR and Vδ1 antigens. Corroboratively, a unique in-frame Vδ1.1JαCα transcript was found in the clone. The clone showed cytotoxic activity and IFN-γ production towards cells expressing HLA-B*3501 pulsed with an HIV Pol-derived epitope peptide (IPLTEEAEL). By flow-cytometric analysis ex vivo using an HLA-B*3501 tetramer, a fraction of Vδ1+CD8+tetramer+ cells was found in peripheral lymphocytes of an HIV-infected patient, indicating the existence of HLA-restricted and HIV-specific Vδ1+ CD8 T cells in vivo. Moreover, retrovirus-mediated transfer of the TCR-encoding genes into TCR-negative hybridoma cells showed that the transduced cells were stained by the tetramer and were activated in response to the Pol peptide, further confirming the ligand specificity of the TCR. Together, these results clearly demonstrate that Vδ1+ αβ TCR are restricted to engaging peptide antigens in the context of classical MHC class I molecules, highlighting the difference in the ligand specificity between Vδ1+ αβ TCR and Vδ1+ γδ TCR.