NKG2A and NKG2C are type II transmembrane proteins with extracellular C-type lectin domains. These proteins heterodimerize with CD94 to form complexes that recognize HLA-E as ligand. The NKG2A/CD94 complex delivers an inhibitory signal resulting from ITIMs within the NKG2A cytoplasmic domain. NKG2C/CD94 provides an activating signal due to association with the ITAM-containing DAP12 adapter protein. These complexes are expressed on NK and T cell subsets.
NKG2D is a type II transmembrane protein with an extracellular C-type lectin domain. It occurs as a disulfide-linked homodimer that associates with either the DAP12 or DAP10 transmembrane adapter proteins. NKG2D is expressed on NK cells and some T cell subsets, where it functions as an activating receptor to trigger cytolytic activity and cytokine secretion. Ligands for human NKG2D include MICA, MICB, and ULBP-1, -2, -3, and -4. Mouse NKG2D ligands include H60, MULT-1, and Rae-1 alpha, beta, gamma, delta, and epsilon.