Study Of Interactions Between SHLA-G1 And Its Receptors-KIR2DL4,ILT2 On NK-92

Human Leukocyte Antigen (HLA)-G is a non-classical MHC-â… molecule that expresses mainly in the cytotrophoblasts at the fetal-maternal interface.. It was initially shown to confer protection to the fetus from her mother's immune system. Expression of HLA-G can be induced in pathological conditions such as transplantation, viral infections, cancer, or autoimmune diseases such as multiple sclerosis showing that beyond its role in fetal-maternal tolerance, HLA-G exerts tolerogenic functions involved in transplant acceptance as well as in tumoral and viral immune escape.NK cells are key lymphocytes of the innate immune system that play a key role in the early defenses against infectious disease and control of cancer cells. NK cells express multi-receptors that specifically recognize HLA-G, which regulate the response of NK cells. It reported that the three receptors of HLA-G, mainly ILT2, ILT4 and KIR2DL4 may involve in this inhibitory cytolysis event, this study focus on the ILT2 and KIR2DL4 which highly express on NK-92 cell line. The results are as follow:1. Recombinant extra-membrane region of HLA-G₁ was obtained by molecular bio-techniques, purified by Ni²⁺ affinity column and renaturated by dialysis.2. Recombinant HLA-G₁ express in Ecoli exert the inhibitory function which can inhibit the cytolysis of NK-92 toward target cells K562-GFP, this inhibition took place through ligand-receptors interaction with ILT2 as well as KIR2DL4.3. The distribution of receptors on NK-92 cells changed a little bit after incubation with recombinant HLA-G₁ confirmed that the function occured through direct ligand-receptor interaction and illuminated that the inhibitory signal pathway initiates from this interaction which may include the reconstruction of the membrane skeleton to transduct the inhibitory signal.These results that HLA-G1 can interact with NK receptors ILT2 and KIR2DL4 then inhibit NK cytolysis provided evidence for the function of HLA-G in pregnancy and tumor immune, as well as for development of new immunosuppressive drug and targeted-drug which will be available treatments for immunological rejection in transplantation.