Human natural killer cell receptors involved in MHC class I recognition are disulfide-linked heterodimers of CD94 and NKG2 subunits

Abstract

CD94 receptors expressed on NK cells have been implicated in the recognition of certain HLA class I allotypes. We now demonstrate that CD94 glycoproteins form disulfide-bonded heterodimers with the NKG2A/B, NKG2C, and NKG2E glycoproteins. NKG2A/B possesses two immunoreceptor tyrosine-based inhibition motif (ITIM) sequences in its cytoplasmic domain, which may be responsible for the inhibitory function of these receptors, whereas other NKG2 proteins lack ITIMs and may potentially transmit positive signals. Structural heterogeneity in the NKG2 gene family and the formation of heterodimers with CD94 provides for the creation of a diverse NK cell repertoire.