Molecular basis of HLA-C recognition by p58 natural killer cell inhibitory receptors.
NK cells express several inhibitory receptors that recognize class I MHC molecules expressed on target cells. The NK cell inhibitory receptors (KIRs) provide a key regulatory function for NK cells via specific interaction with MHC/peptide complexes, but the molecular details for recognition of class I MHC molecules by KIRs still remain unclear. Here we report cDNA cloning and expression of p58 KIRs and a p50 killer cell activatory receptor (KAR) from a Korean blood donor and demonstrate direct binding between recombinant soluble p58 KIRs and recombinant soluble HLA-C molecules. We identified three p58/p50 killer cell receptors (KAR-K1, KIR-K6, and KIR-K7), which are homologous to p50 cl-39, p58 47.11, and p58 cl-6, respectively. Native gel shift assay revealed that p58 KIR-K6 and KIR-K7 bind both HLA-Cw3 and HLA-Cw6 molecules, but p50 KAR-K1 binds neither of the HLA-C molecules. However, binding of HLA-C molecule by p58 KIR is affected by the antigenic peptide bound on the MHC molecule, suggesting that the p58 KIR binding to the HLA-C molecule may be dependent on the peptide. In addition, the binding interaction requires the presence of both p58 Ig domains, suggesting that the binding mode of HLA-C and p58 KIR may have some similarity to that of the neonatal Fc receptor and the Fc fragment of Ab and may be distinct from that of TCR and MHC.
Kim
J
J
Department of Microbiology, Yonsei University College of Medicine, Seoul, Korea.
Chwae
Y J
YJ
Kim
M Y
MY
Choi
I H
IH
Park
J H
JH
Kim
S J
SJ
D000595:Amino Acid Sequence; D000941:Antigens / Q000502:physiology; D001782:Blood Donors; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D015236:HLA-C Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000502:physiology; D007694:Killer Cells, Natural / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology / Q000502:physiology; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3; D055607:Receptors, Natural Killer Cell; D012995:Solubility
D000941:Antigens; D018076:DNA, Complementary; D015236:HLA-C Antigens; D007136:Immunoglobulins; C515078:KIR2DL3 protein, human; D010455:Peptides; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3; D055607:Receptors, Natural Killer Cell