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Title: Hla-g  
Author: World Heritage Encyclopedia
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Subject: Natural killer cell, Human leukocyte antigen, Housekeeping gene, MHC class I, Herpesviridae, Eutherian fetoembryonic defense system (eu-FEDS) hypothesis, HLA-A
Publisher: World Heritage Encyclopedia


Major histocompatibility complex, class I, G
PDB rendering based on 1ydp.
Available structures
PDB Ortholog search: RCSB
HLA-G Gene
RNA expression pattern

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.[1]

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.[1]


HLA-G may play a role in immune tolerance in pregnancy, being expressed in the placenta, while the classical MHC class I genes HLA-A and HLA-B are not.[2] 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.[3]

However, a big 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.[4][5] 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.[6] Also, some higher primates do not show all MHC-G isoforms.[7] 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.[8] 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.[9] 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.[9]


HLA-G has been shown to interact with CD8A.[10][11]


Further reading

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