HLA-G molecule.
Human leukocyte antigen-G (HLA-G) is a non-classical HLA class I molecule, which was first discovered in 1987 by Geraghty and colleagues. While classical HLA class I molecules are expressed on all nucleated cells, the expression of the HLA-G molecule is highly tissue-restricted, such as to placental trophoblast cells. HLA-G binds inhibitory receptors such as leukocyte immunoglobulin-like receptors B1 (LILRB1/ILT2/CD85j) and LILRB2 (ILT4/CD85d), which are widely expressed on immune cells, to suppress a broad range of immune responses. Thus, the expression of HLA-G in placenta protects the fetus from the maternal immune system. On the other hand, emerging studies have shown the relevance of the HLA-G molecule in pathologic conditions, such as transplantation rejection, autoimmunity, and cancer. HLA-G has other unique characteristics, in contrast with classical HLA molecules, including the existence of various forms of HLA-G: several splice variants, subunit-deficient conformations, homodimers, and their combinations have been found. In this review, we highlight the molecular basis for the tolerogenic ability of the HLA-G molecule, especially by LILR recognition of various forms of HLA-G. We also discuss the potential clinical applications of HLA-G molecules.
Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan.
Jun
J
Kamishikiryo
Katsumi
K
Maenaka
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000276:immunology; D005260:Female; D005333:Fetus / Q000276:immunology; D006680:HLA Antigens / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011110:Polymorphism, Genetic / Q000235:genetics; D011247:Pregnancy; D011946:Receptors, Antigen / Q000737:chemistry / Q000276:immunology; D011971:Receptors, Immunologic / Q000737:chemistry / Q000276:immunology; D054340:Receptors, KIR / Q000737:chemistry / Q000276:immunology
D015703:Antigens, CD; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D007166:Immunosuppressive Agents; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011946:Receptors, Antigen; D011971:Receptors, Immunologic; D054340:Receptors, KIR