期刊
CELL RESEARCH
卷 15, 期 3, 页码 176-182出版社
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/sj.cr.7290283
关键词
NK cell; KIR2DL4; HLA-G; receptor
类别
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 alpha 1 domain is an important killer cell Ig-like receptor (KIR) recognition site and the Met(76) and Gln(79) 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 Met(76), Gln(79) mutated to Ala(76,79) in the alpha 1 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 Met(76) and Gln(79) in HLA-G alpha 1 domain plays a critical role in the recognition of KIR2DL4, which could be an explanation for the isoforms of HLA-G, all containing the alpha 1 domain, with the potential to regulate NK functions.
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