Mouse CD 94 / NKG 2 A Is a Natural Killer Cell Receptor for the Nonclassical Major Histocompatibility Complex ( MHC ) Class I Molecule Qa - 1

Natural killer (NK) cells preferentially lyse targets that express reduced levels of major histocompatibility complex (MHC) class I proteins. To date, the only known mouse NK receptors for MHC class I belong to the Ly49 family of C-type lectin homodimers. Here, we report the cloning of mouse NKG2A, and demonstrate it forms an additional and distinct class I receptor, a CD94/NKG2A heterodimer. Using soluble tetramers of the nonclassical class I molecule Qa1 b , we provide direct evidence that CD94/NKG2A recognizes Qa-1 b . We further demonstrate that NK recognition of Qa-1 b results in the inhibition of target cell lysis. Inhibition appears to depend on the presence of Qdm, a Qa-1 b -binding peptide derived from the signal sequences of some classical class I molecules. Mouse NKG2A maps adjacent to CD94 in the heart of the NK complex on mouse chromosome six, one of a small cluster of NKG2-like genes. Our findings suggest that mouse NK cells, like their human counterparts, use multiple mechanisms to survey class I expression on target cells.