NK cell recognition of non-classical HLA class I molecules

NK cells recognize several HLA class IZ, molecules employing both immunoglo bulin-like (Ig-like) and C-type lectin receptors. The CD95/NKG2 and NKG2D l ectin-like molecules, respectively, interact with HLA-E and MICA; CD94/NKG2 A functions as an inhibitory receptor, while CD94/NKG2C and NKG2D trigger N K cell activity. HLA-E predominantly presents nonamers from the lender sequ ences of other class I molecules; a peptide derived from HLA-GI constitutes the highest affinity ligand for both CD94/NKG2 receptors. Members of the I g-like transcript (ILT) or leucocyte Ig-like receptor (LIR) family (ILT2 or LIR-1 and ILT4 or LIR-2), expressed by other leucocyte lineages, interact with a broad spectrum of HLA class In molecules and HLA-G1. Among Ig-like K IRs, the KIR2DL4 (p49) receptor has been shown to specifically recognize HL A-GI; this molecule displays an unusual hybrid structure, sharing features with inhibitory and triggering KIRs.