Residues Met76 and Gln79 in HLA-G alpha1 domain involve in KIR2DL4 recognition.
Human leukocyte antigen-G (HLA-G) has long been speculated as a beneficial factor for a successful pregnancy for its restricted expression on fetal-maternal extravillous cytotrophoblasts and its capability of modulating uterine natural killer cell (uNK) function such as cytotoxicity and cytokine production through NK cell receptors. HLA class I alpha1 domain is an important killer cell Ig-like receptor (KIR) recognition site and the Met76 and Gln79 are unique to HLA-G in this region. NK cell receptor KIR2DL4 is a specific receptor for HLA-G, yet the recognition site on HLA-G remains unknown. In this study, retroviral transduction was applied to express the wild type HLA-G (HLA-wtG), mutant HLA-G (HLA-mG) on the chronic myelogenous leukemia cell line K562 cells and KIR2DL4 molecule on NK-92 cells, respectively. KIR2DL4-IgG Fc fusion protein was generated to determine the binding specificity between KIR2DL4 and HLA-G. Our results showed that residue Met76, Gln79 mutated to Ala76,79 in the alpha1 domain of HLA-G protein could affect the binding affinity between KIR2DL4 and HLA-G, meanwhile, the KIR2DL4 transfected NK-92 cells (NK-92-2DL4) showed a considerably different cytolysis ability against the HLA-wtG and HLA-mG transfected K562 targets. Taken together, our data indicated that residue Met76 and Gln79 in HLA-G alpha1 domain plays a critical role in the recognition of KIR2DL4, which could be an explanation for the isoforms of HLA-G, all containing the a1 domain, with the potential to regulate NK functions.
Yan
Wei Hua
WH
Laboratory of Immunogenetics, Shanghai Second Medical University, 280 South Chongqing Road, Shanghai 200025, China.
Fan
Li An
LA
D001665:Binding Sites; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005973:Glutamine / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008715:Methionine / Q000235:genetics*; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D054340:Receptors, KIR; D054345:Receptors, KIR2DL4; D014162:Transfection
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C515079:KIR2DL4 protein, human; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054345:Receptors, KIR2DL4; D005973:Glutamine; D008715:Methionine