Human leukocyte antigen (HLA)-G is a non-classical major histocompatibility complex (MHC) class I gene belonging to the HLA class I family. The HLA class I family is subdivided into the classical (HLA-Ia) antigens comprised of HLA-A, -B, and -C molecules and the nonclassical (HLA-Ib) group including the HLA-E, -F, and -G molecules. Seven different splice variants of HLA-G have been observed including four membrane isoforms (HLA-G1, HLA-G2, HLA-G3, and HLA-G4) and three soluble isoforms (HLA-G5, HLA-G6 and HLA-G7). Proteolytic processing of HLA-G1 by metalloproteinases (MMPs) such as MMP-2 produces the soluble isoform, shedding HLA-G1. The HLA-G1 and HLA-G5 isoforms share a similar confirmation to the classical MHC class I protein, consisting of three extracellular domains including alpha1, alpha2, and alpha3 associated with Beta-2-microglobulin (B2M). Other HLA-G variants are shorter, missing one or two of the globular domains and are not bound to B2M. HLA-G receptors include KIR2DL4 (CD158d), with the highest affinity for ILT2 (LILRB1, CD85j) and ILT4 (LILRB2, CD85d) (1,2).

Discovered in cytotrophoblasts, HLA-G is involved in fetal maternal immune tolerance and some studies have linked its downregulation with severe preeclampsia (3). HLA-G mediated immune suppression works by impeding cell proliferation, differentiation, cytotoxicity, cytokine secretion and chemotaxis; and activation of regulatory cells and MDSCs or M2 type macrophage. HLA-G is constitutively expressed in immune-privileged sites such as pancreatic islets, mesenchymal stem cells (MSCs) and the cornea. Upregulation of HLA-G occurs in pathological states including cancer, allo-transplantations, viral infections, autoimmune and inflammatory diseases (4). In cancer, HLA-G expression is induced by hypoxia and has been correlated with advanced tumor stage, tumor metastasis, and poor therapeutic response and survival. HLA-G is an attractive tumor associated-antigen (TAA) for immunotherapy and is considered a major immune checkpoint (ICP).

References

1. Loustau, M., Anna, F., Drean, R., Lecomte, M., Langlade-Demoyen, P., & Caumartin, J. (2020). HLA-G Neo-Expression on Tumors. Front Immunol, 11:1685. PMID: 32922387

2. Lin A, Yan WH. (2018) Heterogeneity of HLA-G Expression in Cancers: Facing the Challenges. Front Immunol. 9:2164. PMID: 30319626

3. Djurisic S, Hviid TV. (2014) HLA Class Ib Molecules and Immune Cells in Pregnancy and Preeclampsia. Front Immunol. 5:652. PMID: 25566263

4. Lila N, Rouas-Freiss N, Dausset J, Carpentier A, Carosella ED. (2001) Soluble HLA-G protein secreted by allo-specific CD4+ T cells suppresses the allo-proliferative response: a CD4+ T cell regulatory mechanism. Proc Natl Acad Sci U S A. 98(21):12150-12155. PMID: 11572934

Long Name

Major Histocompatibility Complex, Class I, G

Alternate Names

HLA G, HLA-6.0, HLAG, MHC Class I Antigen G, MHC-G

Gene Symbol

HLA-G

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Product Specific Notices for HLA G Antibody (HLAG/8344R) [Janelia Fluor® 525]

Sold under license from the Howard Hughes Medical Institute, Janelia Research Campus.

This product is for research use only and is not approved for use in humans or in clinical diagnosis. Primary Antibodies are guaranteed for 1 year from date of receipt.

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HLA G Antibody (HLAG/8344R) [Janelia Fluor® 525]

Novus Biologicals, part of Bio-Techne | Catalog # NBP3-20689JF525

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Background: HLA-G