The non-classical MHC class I molecule Qa-1b inhibits classical MHC class I-restricted cytotoxicity of cytotoxic T lymphocytes

The CD94/NKG2A heterodimer is an inhibitory receptor expressed on a subset of mouse NK cells. CD94/NKG2A recognizes the non-classical MHC class I (class Ib) molecule Qa-1b and inhibits NK cytotoxicity. Qa-1b presents a peptide derived from the leader sequence of classical MHC class I molecules. Here, we examined the role of CD94/NKG2A in T cell-mediated cytotoxicity. Soluble tetrameric Qa-1b bound to almost all CD8+, but not CD4+, T cells. This binding seems to be mediated by CD8, because COS cells transfected with CD8 also bound Qa-1b tetramer. Therefore, the expression of CD94/NKG2 in T cells was further examined by single-cell RT-PCR. Most murine CD8+ T cells constitutively expressed CD94 and NKG2A transcripts, whereas they were not detected in CD4+ T cells. Co-expression of Qa-1b and Dk on target cells significantly inhibited cytotoxicity of Dk-specific cytotoxic T lymphocytes generated by mixed lymphocyte reaction, indicating that Qa-1b on antigen-presenting cells interacts with CD94/NKG2A on CD8 T cells and regulates classical MHC class I-restricted cytotoxic T cells. These results suggest a significant role of CD94/NKG2A as an inhibitory receptor on CD8+ T cells.