CLONING OF A MOUSE HOMOLOG OF CD94 EXTENDS THE FAMILY OF C-TYPE LECTINS ON MURINE NATURAL-KILLER-CELLS

Two families of major histocompatibility complex (MHC) class I-specifi c receptors are found on natural killer (NK) cells: immunoglobulin-lik e receptors and C-type lectin receptors. In mice, the latter category is represented by the Ly49 family of receptors, whereas in humans, NK cells express the distantly related CD94, which forms MHC class I-spec ific heterodimers with NKG2 family members. Humans also express the MH C class I-specific p50/p58/p70 family of immunoglobulin-like receptors , but these have not been identified in mice. Hence, there is no known instance of an MHC class I-specific receptor that is expressed by bot h human and murine NK cells. Here we report the cloning of CD94 from t he CB.17 and C57BL/6 strains of mice. Mouse CD94 is 54% identical and 66% similar to human CD94, and is also a member of the C-type lectin s uperfamily. Mouse CD94 is expressed efficiently on the cell surface of cells transiently transfected with the corresponding cDNA, but surfac e CD94 was unable to mediate detectable binding to MHC class I-express ing ConA blasts. Notably, mouse CD94, like human CD94, has a very shor t cytoplasmic tail, suggesting the existence of partner chains that ma y play a role in ligand binding and signaling. Like many other C-type lectins expressed by NK cells, mouse CD94 maps to the NK complex on di stal chromosome 6, synteneic to human CD94. We also demonstrate that m ouse CD94 is highly expressed specifically by mouse NK cells, raising the possibility that mice, like humans, express multiple families of M HC class I-specific receptors on their NK cells. Murine homologs of hu man NKG2 family members have not yet been identified, but we report he re the existence of a murine NKG2D-like sequence that also maps to the murine NK complex near CD94 and Ly49 family members.