PMID- 9764357
OWN - NLM
STAT- MEDLINE
DCOM- 19981202
LR  - 20190921
IS  - 1046-7408 (Print)
IS  - 1046-7408 (Linking)
VI  - 40
IP  - 3
DP  - 1998 Sep
TI  - Molecular and immunologic aspects of the nonclassical HLA class I antigen HLA-G: 
      evidence for an important role in the maternal tolerance of the fetal allograft.
PG  - 136-44
AB  - PROBLEM: Human leukocyte antigen (HLA)-G is a major histocompatibility complex 
      class I antigen, which is referred to as nonclassical because it displays a 
      tissue-restricted distribution in the placenta, a reduced cytoplasmic domain, a 
      limited polymorphism, and several isoforms. The HLA-G antigen is thought to play 
      an essential role during pregnancy by protecting the semi-allogeneic fetus from 
      recognition and destruction by maternal immune cells. METHOD OF STUDY: 
      Alternative splicing of HLA-G mRNA was analyzed by Southern blot of reverse 
      transcriptase-polymerase chain reaction products from trophoblasts of the first 
      trimester of gestation and term placenta. The regulation of HLA-G gene expression 
      was investigated by electrophoretic mobility shift assays using nuclear extracts 
      from cells expressing different levels of HLA-G gene activity. Using polymerase 
      chain reaction-single strand conformational polymorphism and sequencing, we 
      studied HLA-G gene polymorphism in families from the Centre d'Etude du 
      Polymorphisme Humain in Paris. To understand the function of the HLA-G molecule, 
      cytotoxicity assays were carried out with peripheral blood mononuclear cells or 
      polyclonal natural killer effectors cells from 30 different donors against HLA-G1 
      and HLA-G2 transfectants. RESULTS: Four main aspects have been elucidated: 1) The 
      primary transcript of the HLA-G gene is alternatively spliced into five main mRNA 
      forms: HLA-G1 (full length), HLA-G2 (minus exon 3), which encodes a 
      membrane-bound isoform associated with beta-2 microglobulin, HLA-G3 (minus exons 
      3 and 4), HLA-G4 (minus exon 4), and HLA-G5 (plus intron 4), which encodes a 
      soluble form of the HLA-G antigen; 2) specific nuclear factors bind to an 
      important regulatory element located more than 1.2 kb from the HLA-G gene. Three 
      specific complexes are observed in cells that show HLA-G transcriptional activity 
      and an additional factor that could correlate with the repression of HLA-G gene 
      expression that is detected in natural killer cells; 3) we observed an important 
      genomic polymorphism in exon 3 but a very low polymorphism at the protein level; 
      4) HLA-G1 and HLA-G2 transfectants clearly demonstrated that both HLA-G isoforms 
      are capable of inhibiting natural killer lytic activity. CONCLUSION: These 
      results suggest that HLA-G acts as the public ligand for natural killer 
      inhibitory receptors, thus protecting the fetus against maternal rejection.
FAU - Moreau, P
AU  - Moreau P
AD  - Departement de Recherche Medicale, Hopital Saint-Louis, Paris, France.
FAU - Paul, P
AU  - Paul P
FAU - Rouas-Freiss, N
AU  - Rouas-Freiss N
FAU - Kirszenbaum, M
AU  - Kirszenbaum M
FAU - Dausset, J
AU  - Dausset J
FAU - Carosella, E D
AU  - Carosella ED
LA  - eng
PT  - Journal Article
PL  - Denmark
TA  - Am J Reprod Immunol
JT  - American journal of reproductive immunology (New York, N.Y. : 1989)
JID - 8912860
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-G Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Immunologic)
SB  - IM
MH  - Alternative Splicing
MH  - Cytotoxicity, Immunologic
MH  - Female
MH  - Fetal Tissue Transplantation/immunology
MH  - HLA Antigens/biosynthesis/*genetics/*immunology
MH  - HLA-G Antigens
MH  - Histocompatibility Antigens Class I/biosynthesis/*genetics/*immunology
MH  - Humans
MH  - Immune Tolerance/immunology
MH  - Killer Cells, Natural/immunology
MH  - Maternal-Fetal Exchange/immunology
MH  - Polymorphism, Genetic
MH  - Pregnancy
MH  - Protein Isoforms/biosynthesis/genetics/immunology
MH  - RNA, Messenger/metabolism
MH  - Receptors, Immunologic/immunology/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transfection
MH  - Transplantation, Homologous
MH  - Trophoblasts/metabolism
EDAT- 1998/10/09 00:00
MHDA- 1998/10/09 00:01
CRDT- 1998/10/09 00:00
PHST- 1998/10/09 00:00 [pubmed]
PHST- 1998/10/09 00:01 [medline]
PHST- 1998/10/09 00:00 [entrez]
AID - 10.1111/j.1600-0897.1998.tb00405.x [doi]
PST - ppublish
SO  - Am J Reprod Immunol. 1998 Sep;40(3):136-44. doi: 
      10.1111/j.1600-0897.1998.tb00405.x.