Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O95477 (membrane-bound)
 29,236 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human class Ib major histocompatibility complex (MHC) molecule, HLA-G, is unique in its limited polymorphism, high expression in the placenta and generation of multiple transcripts by alternative splicing. The proteins encoded by these transcripts are believed to modulate maternal-fetal immunological relationships during pregnancy. The baboon placenta contains messages encoded by a novel MHC gene, Paan-AG, which is evolutionarily related to the HLA-A locus, but shares unique characteristics with HLA-G. In this study, we show that the Paan-AG message is alternatively spliced to generate at least seven transcripts. One of these transcripts retains intron 4 and encodes a soluble glycoprotein with three external domains and a unique 21-amino-acid sequence at the carboxyl terminus, similar to soluble HLA-G1. This glycoprotein was detected in first trimester placental villous cytotrophoblast and syncytiotrophoblast, and in extravillous cytotrophoblast cells in the basal plate in term placenta. Four of the transcripts ( Paan-AG1, Paan-AG2, Paan-AG3, Paan-AG4) encode membrane-bound class Ib MHC glycoprotein isoforms. Paan-AG1 protein expression was similar to that of sPaan-AG, while Paan-AG2 protein was not detected in these tissues. The other two transcripts ( Paan-AGx and Paan-AGxi) contain a truncated exon 3 and multiple stop codons. Paan-AG1 and Paan-AGx transcripts were detected in a number of non-placental tissues, but these transcripts contained multiple stop codons. Because of the structural similarities and common features of organ-specific expression and splicing of the message, studies on Paan-AG may be of value in dissecting the functions of the class Ib proteins in human pregnancy.
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PMID:Baboon placentas express soluble and membrane-bound Paan-AG proteins encoded by alternatively spliced transcripts of the class Ib major histocompatibility complex gene, Paan-AG. 1207 45

The nonclassical MHC class I locus HLA-G is expressed primarily in the placenta, although other sites of expression have been noted in normal and pathological situations. In addition, soluble HLA-G isoforms have been detected in the serum of pregnant and nonpregnant women as well as men. The rhesus monkey placenta expresses a novel nonclassical MHC class I molecule Mamu-AG, which has features remarkably similar to those of HLA-G. We determined that the rhesus placenta expresses Mamu-AG mRNA (Mamu-AG5), retaining intron 4 as previously noted in HLA-G5. Immunostaining experiments with Ab 16G1 against the soluble HLA-G5 intron 4 peptide demonstrated that an immunoreactive protein(s) was present in the syncytiotrophoblasts of the chorionic villi of the rhesus placenta, within villous cytotrophoblasts, and occasionally within cells of the villous stroma. The Mamu-AG5 mRNA was readily detected in rhesus testis (although not in ejaculated sperm). Whereas an Ab against membrane-bound Mamu-AG stained few cells, primarily in the interstitium of the testis, there was consistent immunostaining for Mamu-AG5 in cells within the seminiferous tubules, which was corroborated by localization of Mamu-AG mRNA by in situ hybridization. While primary spermatocytes were negative, Sertoli cells, spermatocytes, and spermatids were consistently positive for 16G1 immunostaining. The specific recognition of the soluble Mamu-AG isoform was confirmed by Western blotting of Mamu-AG5 expressed in heterologous cells. The results demonstrate that a soluble nonclassical MHC class I molecule is expressed in the rhesus monkey placenta and testis, and confirm and extend the unique homology between HLA-G and the rhesus nonclassical molecule Mamu-AG.
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PMID:A soluble isoform of the rhesus monkey nonclassical MHC class I molecule Mamu-AG is expressed in the placenta and the testis. 1209 69

Several members of the immunoglobulin-like transcript (ILT), also called leukocyte immunoglobulin-like receptor (LIR), family of transmembrane proteins have been identified as receptors for class I HLA molecules and transduce inhibitory signals to leukocytes upon binding of these ligands. The ligands for ILT2 (LIR1/CD85j) and ILT4 (LIR2/CD85d) include HLA-A, -B, and -G, the last of which is highly expressed in fetal trophoblast cells in both membrane-bound and soluble isoforms. To investigate the potential of fetally-derived HLA class I molecules to interact with maternal macrophages through these receptors, we examined the expression patterns of ILT2 and ILT4 in decidual macrophages. Highly purified populations of decidual macrophages were obtained by fluorescence activated cell sorting and were examined by RT-PCR for these messages. Analysis of mRNA from first trimester and term macrophages, as well as the monocyte cell line U937, resulted in amplicons of similar size to those expected for ILT2 and ILT4. Sequence analysis of the amplicons revealed that the messages from decidual macrophages corresponded to ILT2 and ILT4 messages. The message amplified from the U937 cells using the ILT2 primers was also found to be identical to ILT2; however, sequence analysis revealed that the ILT4 message amplified from these cells is a truncated form of the message. Dual label flow cytometry confirmed the expression of ILT2 and ILT4 on CD14-positive first trimester decidual macrophages and U937 cells. These results reveal that inhibitory HLA receptors are expressed in decidual macrophages and suggest that HLA-G may deliver negative signals to maternal decidual macrophages through interaction with these receptors.
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PMID:Decidual macrophages are potentially susceptible to inhibition by class Ia and class Ib HLA molecules. 1210 80

HLA-G is a non-classical major histocompatibility complex class I molecule that differs from the classical HLA I class molecules by (1) a limited polymorphism, (2) a tissue-restricted distribution and (3) a transcription of spliced messenger RNAs encoding for at least four membrane-bound and two soluble HLA-G isoforms. Extensive studies over the past few years have identified HLA-G as a molecule involved in immune tolerance. In this review, attempts were made to summarize the current state of knowledge of the polymorphisms, expression, function, the effects of HLA-G on immuno-associated disease, evolution of HLA-G and its utility in disease therapy.
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PMID:[Genetic polymorphisms, function and clinical effect of HLA-G]. 1217 Apr 78

Data are presented on the intracellular trafficking of HLA-G protein, taking the unique features of this non-classical molecule into consideration: the existence of seven isoforms resulting from alternative splicing (HLA-G1 to G7), and reduced tail length compared with HLA class I antigens. Biochemical studies and analysis of viral strategies for escaping the host immune system led to the demonstration that (i) both the membrane-bound (HLA-G1) and the soluble (HLA-G5) forms of the molecule require peptide association for cell surface expression, using TAP-dependent or TAP-independent pathways; (ii) peptide loading onto the HLA-G protein plays a critical role in controlling the quality of the molecule reaching the cell surface; (iii) surface expression of truncated HLA-G molecules is possible, and (iv) HLA-G expression may be restricted to soluble HLA-G5. These data reveal that HLA-G presents specific cell trafficking pathways and strongly support the contention that the primary function of HLA-G is as of an inhibitor ligand for immune-competent cells.
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PMID:HLA-G protein processing and transport to the cell surface. 1244 Jul 68

Nonclassical major histocompatibility complex (MHC) class I human leukocyte antigen E (HLA-E) and HLA-G molecules differ from classical ones by specific patterns of transcription, protein expression, and immunotolerant functions. The HLA-G molecule can be expressed as four membrane-bound (HLA-G1 to -G4) and three soluble (HLA-G5 to -G7) proteins upon alternative splicing of its primary transcript. In this study, we describe a new set of monoclonal antibodies (mAbs) called MEM-G/01, -G/04, -G/09, -G/13, MEM-E/02, and -E/06 recognizing HLA-G or HLA-E. The pattern of reactivity of these mAbs were analyzed on transfected cells by flow cytometry, Western blotting, and immunochemistry. MEM-G/09 and -G/13 mAbs react exclusively with native HLA-G1 molecules, as the 87G mAb. MEM-G/01 recognizes (similar to the 4H84 mAb) the denatured HLA-G heavy chain of all isoforms, whereas MEM-G/04 recognizes selectively denatured HLA-G1, -G2, and -G5 isoforms. MEM-E/02 and -E/06 mAbs bind the denatured and cell surface HLA-E molecules, respectively. These mAbs were then used to analyze the expression of HLA-G and HLA-E on freshly isolated cytotrophoblast cells, on the JEG-3 placental tumor cell line, and on cryopreserved and paraffin-embedded serial sections of trophoblast tissue. These new mAbs represent valuable tools to study the expression of HLA-G and HLA-E molecules in cells and tissues under normal and pathologic conditions.
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PMID:Characterization of monoclonal antibodies recognizing HLA-G or HLA-E: new tools to analyze the expression of nonclassical HLA class I molecules. 1259 Sep 76

During pregnancy, the human extra-villous trophoblast in the contact zone between maternal and fetal tissue in the placenta does not express the classical MHC class I and II molecules. Instead, HLA-G and -C, and possibly HLA-E, are expressed. HLA-G may modulate the immunological relationship between mother and fetus in several ways. Finally, the expression of membrane-bound HLA-G and soluble HLA-G has been proposed to influence the outcome of pregnancy, and an aberrant HLA-G expression in pre-eclamptic placentas and spontaneous abortions has been reported. Here, an association between certain HLA-G polymorphisms and the mRNA levels of the different alternatively spliced HLA-G isoforms in first trimester trophoblast cell populations is reported. Several alternatively spliced HLA-G mRNA isoforms, including a 14-bp polymorphism in the 3'UTR end (exon 8) of the HLA-G gene, are expressed at a significantly lower level than the corresponding HLA-G mRNA isoforms with the 14-bp sequence deleted. Furthermore, characteristic HLA-G mRNA isoform expression patterns were associated with specific HLA-G genotypes and alleles. In the HLA-G*01012 and - G*01013 alleles that include the 14-bp sequence, an additional alternative splicing was observed, with the first 92-bp of exon 8 spliced out. This was most pronounced in HLA-G genotypes with G*01013. These findings may have functional implications for the recent reports of aberrant HLA-G expression and reproductive success.
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PMID:HLA-G allelic variants are associated with differences in the HLA-G mRNA isoform profile and HLA-G mRNA levels. 1271 63

HLA-G differs from the other MHC class I genes. This includes a unique promoter region, a restricted constitutive tissular distribution, the translation of different membrane-bound and soluble isoforms, a shortened cytoplasmic tail and a minimal polymorphim. Soluble HLA-G1 is an immunosuppressive molecule inducing apoptosis of activated CD8(+) T cells and down-modulating CD4(+) T cell proliferation. Soluble HLA-G1 may also contribute to the control of implantation.
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PMID:Soluble HLA-G1 at the materno-foetal interface--a review. 1284 8

During pregnancy the fetus represents a semi-allograft. Both membrane-bound and soluble forms of the nonclassic human leukocyte antigen (HLA)-G protect the fetus from maternal immune attack. To assess the relevance of soluble HLA-G (sHLA-G) levels in the maternal circulation for the occurrence of characteristic pregnancy disorders, we analyzed sHLA-G plasma levels of women with normal and pathological pregnancies. Compared to normal pregnancy, significantly increased sHLA-G levels were detected in women delivered preterm because of intrauterine activation (uncontrollable labor, rupture of fetal membranes, cervical insufficiency) and women with Hemolysis, Elevated Liver enzymes, Low Platelet count (HELLP) syndrome. Contrary to these disorders, the sHLA-G levels in women with placental abruption were more than three times lower than in normal pregnancy (p < .0001). Nonparametric discriminant analysis showed that women with sHLA-G levels below 9.95 ng/mL had a relative risk of 7.12 for the development of placental abruption during further course of pregnancy. These results suggest that the occurrence of pregnancy-associated diseases is strongly influenced by maternal sHLA-G plasma levels.
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PMID:Placental abruption is associated with decreased maternal plasma levels of soluble HLA-G. 1295 23

HLA-G is a non-classical major histocompatibility complex class I gene, exhibiting unique structure and whose tissue distribution is mainly restricted to the placenta. Its function contributes to modulate local placental immunity during pregnancy. Major structural characteristics are as follows: a unique promoter region, distinct from the other MHC class I promoters described to date, mRNA alternatively spliced into a variety of membrane-bound isoforms and two major soluble forms. HLA-G expression in the placenta is found mainly in extravillous cytotrophoblast that invade decidual tissue and maternal spiral arteries as well as villous cytotrophoblast (soluble form). Soluble HLA-G1 isoforms might play an important role in the embryonic implantation. HLA-G was also found to induce apoptosis of activated CD8(+) T cells. HLA-G also modulates cytokine secretion of NK cells upon interaction with specific receptors.
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PMID:[HLA-G and local placental immunity]. 1449 28


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