The non-classical MHC class I molecule Qa-1(b) 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/KG2A recognizes the non-classical MHC class I(class Ib) molecule Qa-1(b) and inhibits NK cytotoxicity, Qa-1(b) presents a pept ide derived from the leader sequence of classical MHC class 1 molecules. He re, we examined the role of CD94/NKG2A in T cell-mediated cytotoxicity, Sol uble tetrameric Qa-lb bound to almost all CD8(+), but not CD4(+), T cells. This binding seems to be mediated by GD8, because COS cells transfected wit h GD8 also bound Qa-1(b) tetramer, Therefore, the expression of CD94/NKG2 i n T cells was further examined by single-cell RT-PGR. Most murine CD8(+) T cells constitutively expressed CD94 and NKG2A transcripts, whereas they wer e not detected in CD4(+) T cells, Go-expression of Qa-1(b) and D-k On targe t cells significantly inhibited cytotoxicity of D-k-specific cytotoxic T ly mphocytes generated by mixed lymphocyte reaction, indicating that Qa-lb on antigen-presenting cells interacts with CD94/NKG2A on GD8 T cells and regul ates classical MHC class I-restricted cytotoxic T cells. These results sugg est a significant role of CD94/NKG2A as an inhibitory receptor on CD8(+) T cells.