STRUCTURE AND FUNCTION OF THE CD94 C-TYPE LECTIN RECEPTOR COMPLEX INVOLVED IN RECOGNITION OF HLA CLASS-I MOLECULES

A multigene family of immunoglobulin superfamily (Ig-SF) killer cell i nhibitory receptors (KIRs) specifically recognize HLA class I molecule s, while the interaction with H-2 products is mediated by members of t he murine Ly49 C-type lectin family. A common structural feature of th ese receptors with inhibitory function is the presence of cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that couple th em to SHP phosphatases. Strong support for the involvement of the CD94 C-type lectin receptor complex in NK cell-mediated recognition of Bw6 + HLA-B, HLA-A and HLA-C alleles has been obtained. The cloned CD94 mo lecule covalently assembles with at least two different glycoproteins (43 kDa and 39 kDa) to form functional receptors. NK cells inhibited u pon HLA recognition express the CD94/p43 dimer, whose specificity for HLA molecules partially overlaps the Ig-SF receptor system. By contras t, NK clones bearing the homologous CD94/p39 receptor are triggered up on its ligation by CD94-specific mAbs. Remarkably, a set of Ig-SF rece ptors (p50) homologous to p58 KIRs also display an activating function . CD94-associated molecules belong to the NKG2 family of C-type lectin s; the NKG2-A gene encodes for the p43 subunit, which contains cytopla smic ITIMS. Expression of the different CD94 heterodimeric receptors w ill enable precise analysis of their putative interaction with HLA cla ss I molecules.