Cutting Edge: Requirement of Class I Signal Sequence-Derived Peptides for HLA-E Recognition by a Mouse Cytotoxic T Cell Clone

The human nonclassical MHC class I molecule HLA-E has recently been shown to act as a major ligand for NK cell inhibitory receptors. Using HLA-E-expressing transgenic mice, we produced a cytotoxic T cell clone that specifically recognizes the HLA-E molecule. We report here that this T cell clone lyses HLA-E-transfected RMA-S target cells sensitized with synthetic class I signal sequence nonamers. Moreover, this T cell clone lyses human EBV-infected B lymphocytes, PHA blasts, and PBL, formally demonstrating the surface expression of HLA-E/class I signal-derived peptide complex on human cells. Furthermore, these data show that HLA-E complexed with class I signal sequence-derived peptides is not only a ligand for NK cell inhibitory receptors, but can also trigger cytotoxic T cells (CTL).