HLA-G Protein, Human (His-SUMO)

HLA-G, a non-classical major histocompatibility class Ib molecule, plays a crucial role in immune regulation at the maternal-fetal interface. In association with B2M/beta-2 microglobulin, it forms a complex that selectively binds a limited repertoire of nonamer self-peptides derived from intracellular proteins, including histones and ribosomal proteins. This peptide-bound HLA-G-B2M complex acts as a ligand for inhibitory/activating KIR2DL4, LILRB1, and LILRB2 receptors on uterine immune cells, fostering fetal development while maintaining maternal-fetal tolerance. Interactions with KIR2DL4 and LILRB1 receptors trigger NK cell senescence-associated secretory phenotype, promoting vascular remodeling and fetal growth during early pregnancy. Moreover, HLA-G's engagement with LILRB2 induces the differentiation of type 1 regulatory T cells and myeloid-derived suppressor cells, actively contributing to the maintenance of maternal-fetal tolerance. Additionally, HLA-G may play a role in balancing tolerance and antiviral immunity by modulating the effector functions of NK cells, CD8+ T cells, and B cells. Furthermore, it negatively regulates NK cell- and CD8+ T cell-mediated cytotoxicity, highlighting its multifaceted role in immune regulation at the maternal-fetal interface.