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Query: UNIPROT:O95477 (membrane-bound)
 29,236 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HLA-G is a non-classical MHC class I molecule involved in immune tolerance. We present our results concerning the effects of HLA-G on the cellular immune response, where it impairs both NK and T cell functions. We describe the NK inhibitory properties of HLA-G ex vivo, demonstrating its role in materno-fetal tolerance, which is supported by our in vitro studies using membrane-bound HLA-G1- and HLA-G2-transfected cells and a full-length soluble HLA-G molecule. We also report how HLA-G interacts at the T cell level, here exemplified by its inhibitory effect on both T cell allogeneic proliferative and Ag-specific CTL responses.
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PMID:The immunotolerance role of HLA-G. 1009 45

Nonclassical MHC class I HLA-G antigen expression is tissue specific and is thought to play a role in tolerance of the semiallogeneic fetus by the maternal immune system. Ectopic expression of HLA-G by tumor cells provides them with an additional mechanism of escape from immunosurveillance by host cytotoxic effector mechanisms. The aim of this study was to assess the expression of nonclassical HLA-G antigens in ex vivo human melanoma biopsies. HLA-G mRNA levels corresponding to both membrane-bound and soluble protein isoforms were analyzed in tumor specimens obtained from primary or metastatic melanomas of 23 patients. High levels of HLA-G transcription were detected in tumor specimens in 5 of 23 patients and found to be comparable in both lymph node and skin metastases. HLA-G mRNA transcript levels at tumor sites in 18 of these patients were compared with those in samples of their own healthy skin and were higher in the tumor tissue in 12 patients. Differential expression of mRNA transcripts corresponding to soluble and membrane-bound HLA-G was also observed in some tumor biopsies. HLA-G protein expression was detected in tumors that exhibited high levels of HLA-G transcription by immunofluorescence of frozen sections and Western blot analysis of both tumor and healthy skin biopsies, using anti-HLA-G-specific monoclonal antibodies. This work provides evidence that HLA-G gene transcription and protein expression can be up-regulated ex vivo in melanoma. Our finding that several of the tumors studied expressed high levels of HLA-G provides additional clues as to how a tumor can be selected in vivo to escape from cytotoxic antitumor responses, constituting a new parameter to be considered in the design of therapeutic approaches aimed at enhancing antitumor immune responses.
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PMID:Heterogeneity of HLA-G gene transcription and protein expression in malignant melanoma biopsies. 1021 6

HLA-G is a nonclassical major histocompatibility complex class I molecule selectively expressed on cytotrophoblasts at the fetal-maternal interface, where it plays a role in materno-fetal tolerance. In contrast to classical HLA-A, -B and -C class I molecules, HLA-G is characterized by (i) a tissue-restricted distribution, (ii) a limited polymorphism and (iii) 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 effects of HLA-G on both natural killer and T cell functions and their implications in materno-fetal tolerance and tumor immunosurveillance.
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PMID:Immunotolerant functions of HLA-G. 1022 53

The human MHC class Ib gene HLA-G is transcribed and translated in different placental cell subpopulations during pregnancy. In addition to this restricted tissue distribution, HLA-G proteins were also recently detected in the thymus of HLA-G transgenic mice, as well as in some human thymic epithelial cells (TEC). There was a need to further define the phenotype of the HLA-G-expressing cells in the human thymus as well as the type of translated forms that they produce. Using several HLA-G-specific mAb and immunohistochemistry performed on cryosections of human thymi at different ages, we found that the HLA-G-expressing cells are present on medullary cells exhibiting the epithelial morphological type 6. Co-localization experiments performed by double or triple immunofluorescence staining demonstrate that these HLA-G-expressing cells express various cytokeratins, epithelial cell markers but not the CD83 dendritic cell marker. We further show by ELISA measurements that a subset of primary cultured human TEC also expresses soluble HLA-G. Therefore, HLA-G protein tissue distribution is not restricted solely to placental cells. A subpopulation of medullary TEC also expresses HLA-G both at their cell surface and in secreted form, raising the question of the functional significance of such MHC class Ib molecules. Whether thymic soluble and/or membrane-bound HLA-G contribute to inhibit NK cells or to a negative selection of autoreactive T cells which could be harmful in case of pregnancy and/or to a positive selection of viral peptides/HLA-G-restricted CD8(+) T cells remains to be demonstrated.
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PMID:HLA-G in the human thymus: a subpopulation of medullary epithelial but not CD83(+) dendritic cells expresses HLA-G as a membrane-bound and soluble protein. 1036 Sep 62

In contrast to HLA-A and -B class Ia genes that are down-regulated in human trophoblast cells, HLA-G class Ib molecules are expressed in the placenta throughout gestation. In addition to extravillous cytotrophoblast that invade the decidua basalis essentially, HLA-G was also observed in endothelial cells of fetal vessels in the chorionic villi as well as in amnion cells and amniotic fluid. Both membrane-bound and soluble HLA-G isoforms have been detected. In view of the recently published functional data showing that HLA-G: (i) has the capability to bind and present peptides; (ii) is recognized by at least three different killing inhibitory receptors; and (iii) is a regulator of HLA-E expression, we can predict that such functions are likely to be exerted by extravillous cytotrophoblast. Of particular importance will be the anti-viral function of HLA-G at this materno-fetal interface, knowing that HLA-G was shown to be expressed by thymic medullary epithelial cells. In addition to these immunological functions, due to its presence on chorionic fetal endothelial cells, we hypothesize that HLA-G could also be a regulator of chorionic villous angiogenesis. Finally, soluble HLA-G isoforms may act as specific immunosuppressors during pregnancy.
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PMID:Placental HLA-G protein expression in vivo: where and what for? 1043 7

This report demonstrates that both membrane-bound and soluble HLA-G isoforms are present in primary cultured human thymic epithelial cells (TEC). HLA-G transcriptional isoforms have been detected by RT-PCR, using different sets of HLA-G specific primers. A flow cytometry analysis, using two anti-HLA-G mAbs, namely 87G and BFL.1, revealed the presence of HLA-G translated products at the cell surface of a subpopulation of TEC. Finally, it was shown that HLA-G soluble forms were secreted in TEC culture supernatant, using a sandwich ELISA with BFL.1 and W6/32 mAbs. These results confirm and extent those previously described showing that HLA-G expressing cells were detectable by immunohistochemistry in thymic medullary epithelial cells.
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PMID:Primary cultured human thymic epithelial cells express both membrane-bound and soluble HLA-G translated products. 1047 58

In contrast to HLA class Ia, the HLA-G class Ib transcripts can be alternativeley spliced to yield several isoforms including four potentially membrane-bound variants, namely HLA-G1, -G2, -G3 and G4. It is so far unclear whether each of these splice variants lacking one or two external domains is properly translated and expressed at the cell surface. We used targeted Enhanced Green Fluorescence Protein (EGFP)-HLA-G fusion cDNA to track HLA-G isoform expression in living murine (L-human beta2m) and human (JAR) transiently transfected cells. It was demonstrated that the four HLA-G1, -G2, -G3, and -G4 isoforms were translated in these transfectants by the means of (i) Western blotting analysis, using an anti-EGFP mAb; (ii) intracellular double labeling flow cytometry analysis, using the EGFP natural fluorescence and phycoerythrin-labeled HCA2 anti-HLA-G mAb; and (iii) immunocytochemistry on isolated acetone fixed transfectants with the use of different anti-HLA-G mAbs. Cell surface flow cytometry analysis using the HCA2 mAb revealed that only the HLA-G1 isoform was expressed as a membrane-bound protein. Two color confocal microscopy performed on fixed, permeabilized cells further showed that the EGFP green fluorescence co-localized with anti-calnexin rhodamine fluorescence in the four HLA-G isoform transfectants but only in HLA-G1 transfectant was the green EGFP fluorescence also detectable at the outer part of the cells, suggesting that the HLA-G2, -G3, and G4 were retained in the endoplasmic reticulum. Such intracellular retention of the three shorter forms of HLA-G suggest that they may play a role in regulating cell surface expression either of the full length HLA-G1 form or of HLA-E.
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PMID:The full length HLA-G1 and no other alternative form of HLA-G is expressed at the cell surface of transfected cells. 1068 11

HLA-G is a nonclassical class I MHC molecule of unknown function expressed on human invasive trophoblast. In trophoblast cells, HLA-G mRNA is alternatively spliced into a variety of forms which are predicted to encode a full length membrane-bound form, three short membrane-bound isoforms and two soluble isoforms. The aim of this study was to determine which of these protein isoforms are translated, which are expressed on the cell surface and which are secreted. Artificial cDNAs encoding the isoforms were generated by PCR mutagenesis, ligated to an epitope tag and transfected into a human cell line capable of expressing MHC class I. Protein products of appropriate sizes were detected in cells transfected with cDNAs encoding all membrane-bound forms, but surface biotinylation studies indicated that only full length membrane-bound HLA-G was present at the cell surface. Full length HLA-G was also detected by surface antibody binding and flow cytometry. Soluble HLA-G1 was detected in cells transfected with the appropriate cDNA only after treatment with monensin, which inhibits transport of glycoproteins through the Golgi apparatus. These results suggest that full length HLA-G, but not short HLA-G isoforms can be expressed on the surface of human cells and that soluble HLA-G is rapidly secreted. Thus, it is likely that the full length membrane-bound and soluble forms of HLA-G are the only biologically active forms to which the mother is exposed.
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PMID:The short forms of HLA-G are unlikely to play a role in pregnancy because they are not expressed at the cell surface. 1077 86

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.
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PMID:HLA-G polymorphisms and molecule function--questions and more questions--a review. 1083 Nov 30

HLA-G is a non-classical major histocompatibility complex class I molecule that differs from the classical HLA-A, -B and -C molecules by (i) alternative splicing of mRNAs encoding for at least four membrane-bound and two soluble HLA-G isoforms, (ii) a limited polymorphism, and (iii) a tissue-restricted distribution. Studies over the past few years have elucidated the function of HLA-G demonstrating inhibition of both NK cell- and T cell-mediated cytolysis. Furthermore, aside from its expression during pregnancy, we have shown that HLA-G is also expressed in solid tumor cells (i.e. human melanoma cell lines and ex vivo melanoma biopsies). Here we present a review of the current state of knowledge of the immunotolerant functions of HLA-G and their implications in materno-fetal tolerance and tumor immunosurveillance.
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PMID:HLA-G promotes immune tolerance. 1084 Dec 84


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