HLA-G

3KYO, 1YDP, 2D31, 2DYP, 3BZE, 3CDG, 3CII, 3KYN313514991ENSG00000235346ENSG00000235680ENSG00000206506ENSMUSG00000016206P17693Q31093NM_002127NM_001363567NM_013819NP_002118NP_001350496NP_038847HLA-G histocompatibility antigen, class I, G, also known as human leukocyte antigen G (HLA-G), is a protein that in humans is encoded by the HLA-G gene.1ydp: 1.9A crystal structure of HLA-G2d31: Crystal structure of disulfide-linked HLA-G dimer2dyp: Crystal Structure of LILRB2(LIR2/ILT4/CD85d) complexed with HLA-G HLA-G histocompatibility antigen, class I, G, also known as human leukocyte antigen G (HLA-G), is a protein that in humans is encoded by the HLA-G gene. HLA-G belongs to the HLA nonclassical class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. HLA-G is expressed on fetal derived placental cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domain, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exon 6 encodes the cytoplasmic tail. Exon 7 and 8 are not translated due to a stop codon present in exon 6. HLA-G may play a role in immune tolerance in pregnancy, being expressed in the placenta by extravillous trophoblast cells (EVT), while the classical MHC class I genes (HLA-A and HLA-B) are not. As HLA-G was first identified in placenta samples, many studies have evaluated its role in pregnancy disorders, such as preeclampsia and recurrent pregnancy loss. its downregulation is related to HLA-A and -B downregulation results in protection from cytotoxic T cell responses, but would in theory result in a missing self response by natural killer cells. HLA-G is a ligand for NK cell inhibitory receptor KIR2DL4, and therefore expression of this HLA by the trophoblast defends it against NK cell-mediated death. However, a large family with several members bearing only 'null' HLA-G alleles has been found. None of these homozygous subjects have pregnancy or birth difficulties; nor do they present immunodeficiencies, autoimmune diseases, or tumors. It is striking that this 'null' allele (HLA-G*01:05N), while it is quite frequent in some populations, like in Iranians, it is almost absent in some Amerindian populations. Also, some higher primates do not show all MHC-G isoforms. In addition, Cercopithecinae middle-sized Old World monkeys do not bear full MHC-G molecules since all of these monkeys present stop codons at MHC-G DNA. All of these anomalies must be studied. The presence of soluble HLA-G (sHLA-G) in embryos is associated with better pregnancy rates. In order to optimize pregnancy rates, there is significant evidence that a morphological scoring system is the best strategy for the selection of embryos. However, presence of soluble HLA-G might be considered as a second parameter if a choice has to be made between embryos of morphologically equal quality. HLA-G has been shown to interact with CD8A.