HLA-G polymorphisms and molecule function--questions and more questions--a review.
Human leukocyte antigen (HLA)-G is a non-classical HLA-class I antigen which is predominantly expressed on invasive trophoblastic cells and is postulated to be a mediator of maternal-fetal tolerance. HLA-G interacts with NK cells, can present nonamer peptides and binds CD8 in an analogous manner to classical HLA-I. The HLA-G protein exists in soluble and membrane-bound isoforms generated through alternative splicing. Although initially considered to be non-polymorphic, variations of the HLA-G DNA sequence have been reported which led to the definition of a limited number of HLA-G alleles including the Null-allele G*0105N. Whereas the HLA-G DNA sequence shows a high degree of conservation in positions which are essential for classical HLA-I molecule functions, polymorphic sites in HLA-G are not congruent with sites of high nucleotide variability in classical HLA. The identification of two females with recurrent spontaneous abortions who are homozygous for the G*0105N Null-allele re-opens the discussion about the role of HLA-G in pregnancy and underlines the need of a systematic analysis of the different hypotheses of HLA-G function in vivo.
van der Ven
K
K
University of Bonn, Department of Obstetrics and Gynecology, Germany.
Pfeiffer
K
K
Skrablin
S
S
D000483:Alleles; D017398:Alternative Splicing; D005260:Female; D005805:Genes, MHC Class I; D006680:HLA Antigens / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology; D011255:Pregnancy Maintenance / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell