HLA class I-restricted recognition of an HIV-derived epitope peptide by a human T cell receptor alpha chain having a...

A subset of human peripheral alpha beta T cells have been shown to express TCR alpha chains containing Vdelta1 segments, although what antigens the Vdelta1(+) alpha beta T cells recognize via these TCR is not known yet. We eventually established a human CD8 T cell clone that expressed alpha beta TCR and Vdelta1 antigens. Corroboratively, a unique in-frame Vdelta1. 1JalphaCalpha transcript was found in the clone. The clone showed cytotoxic activity and IFN-gamma 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 Vdelta1(+)CD8(+)tetramer(+) cells was found in peripheral lymphocytes of an HIV-infected patient, indicating the existence of HLA-restricted and HIV-specific Vdelta1(+) 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 Vdelta1(+) alpha beta TCR are restricted to engaging peptide antigens in the context of classical MHC class I molecules, highlighting the difference in the ligand specificity between Vdelta1(+) alpha beta TCR and Vdelta1(+) gamma delta TCR.