[Isoform 1]: Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface (PubMed:
23184984, PubMed:
29262349, PubMed:
19304799). In complex with B2M/beta-2 microglobulin binds a limited repertoire of nonamer self-peptides derived from intracellular proteins including histones and ribosomal proteins (PubMed:
7584149, PubMed:
8805247). Peptide-bound HLA-G-B2M complex acts as a ligand for inhibitory/activating KIR2DL4, LILRB1 and LILRB2 receptors on uterine immune cells to promote fetal development while maintaining maternal- fetal tolerance (PubMed:
23184984, PubMed:
29262349, PubMed:
16366734, PubMed:
19304799, PubMed:
20448110, PubMed:
27859042). Upon interaction with KIR2DL4 and LILRB1 receptors on decidual NK cells, it triggers NK cell senescence-associated secretory phenotype as a molecular switch to promote vascular remodeling and fetal growth in early pregnancy (PubMed:
23184984, PubMed:
29262349, PubMed:
16366734, PubMed:
19304799). Through interaction with KIR2DL4 receptor on decidual macrophages induces proinflammatory cytokine production mainly associated with tissue remodeling (PubMed:
19304799). Through interaction with LILRB2 receptor triggers differentiation of type 1 regulatory T cells and myeloid-derived suppressor cells, both of which actively maintain maternal-fetal tolerance (PubMed:
20448110, PubMed:
27859042). May play a role in balancing tolerance and antiviral-immunity at maternal-fetal interface by keeping in check the effector functions of NK, CD8+ T cells and B cells (PubMed:
10190900, PubMed:
11290782, PubMed:
24453251). Reprograms B cells toward an immune suppressive phenotype via LILRB1 (PubMed:
24453251). May induce immune activation/suppression via intercellular membrane transfer (trogocytosis), likely enabling interaction with KIR2DL4, which resides mostly in endosomes (PubMed:
20179272, PubMed:
26460007). Through interaction with the inhibitory receptor CD160 on endothelial cells may control angiogenesis in immune privileged sites (PubMed:
16809620).