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1.
Moreau P Rousseau P Rouas-Freiss N Le Discorde M Dausset J Carosella ED 《Cellular and molecular life sciences : CMLS》2002,59(9):1460-1466
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.
Received 4 June 2002; accepted 2 July 2002
RID="*"
ID="*"Corresponding author. 相似文献
2.
Kiave-Yune HoWangYin Estibaliz Alegre Marina Daouya Benoit Favier Edgardo D. Carosella Joel LeMaoult 《Cellular and molecular life sciences : CMLS》2010,67(7):1133-1145
Trogocytosis is the uptake of membranes from one cell by another. Trogocytosis has been demonstrated for monocytes, B cells,
T cells, and NK cells. The acquisition of the tolerogenic molecule HLA-G by T cells and NK cells makes them behave as regulatory
cells. We investigated here whether HLA-G, which is expressed by tumor cells in vivo, could be acquired by monocytes and if
this transfer could have functional consequences. We demonstrate that resting, and even more so, activated monocytes efficiently
acquire membrane-bound HLA-G from HLA-G tumor cells by trogocytosis. However, we demonstrate that HLA-G quickly disappears
from the surface of the monocytes in contrast to the HLA-G acquired by T cells. Consequently, HLA-Gacq+ monocytes do not reliably inhibit the on-going proliferation of autologous activated T cells and do not inhibit their cytokine
production. Thus, we show that the acquirer cell may control the functional outcome of trogocytosis. 相似文献
3.
Amiot L Ferrone S Grosse-Wilde H Seliger B 《Cellular and molecular life sciences : CMLS》2011,68(3):417-431
Although the expression of the non-classical HLA class I molecule HLA-G was first reported to be restricted to the fetal–maternal
interface on the extravillous cytotrophoblasts, the distribution of HLA-G in normal tissues appears broader than originally
described. HLA-G expression was found in embryonic tissues, in adult immune privileged organs, and in cells of the hematopoietic
lineage. More interestingly, under pathophysiological conditions HLA-G antigens may be expressed on various types of malignant
cells suggesting that HLA-G antigen expression is one strategy used by tumor cells to escape immune surveillance. In this
article, we will focus on HLA-G expression in cancers of distinct histology and its association with the clinical course of
diseases, on the underlying molecular mechanisms of impaired HLA-G expression, on the immune tolerant function of HLA-G in
tumors, and on the use of membrane-bound and soluble HLA-G as a diagnostic or prognostic biomarker to identify tumors and
to monitor disease stage, as well as on the use of HLA-G as a novel therapeutic target in cancer. 相似文献
4.
Carosella ED Gregori S Rouas-Freiss N LeMaoult J Menier C Favier B 《Cellular and molecular life sciences : CMLS》2011,68(3):353-368
The non-classical HLA class I molecule HLA-G was initially shown to play a major role in feto–maternal tolerance. Since this
discovery, it has been established that HLA-G is a tolerogenic molecule which participates to the control of the immune response.
In this review, we summarize the recent advances on (1) the multiple structures of HLA-G, which are closely associated with
their role in the inhibition of NK cell cytotoxicity, (2) the factors that regulate the expression of HLA-G and its receptors,
(3) the mechanism of action of HLA-G at the immunological synapse and through trogocytosis, and (4) the generation of suppressive
cells through HLA-G. Moreover, we also review recent findings on the non-immunological functions of HLA-G in erythropoiesis
and angiogenesis. 相似文献
5.
Deschaseaux F Delgado D Pistoia V Giuliani M Morandi F Durrbach A 《Cellular and molecular life sciences : CMLS》2011,68(3):397-404
HLA-G plays a particular role during pregnancy in which its expression at the feto–maternal barrier participates into the
tolerance of the allogenic foetus. HLA-G has also been demonstrated to be expressed in some transplanted patients, suggesting
that it regulates the allogenic response. In vitro data indicate that HLA-G modulates NK cells, T cells, and DC maturation
through its interactions with various inhibitory receptors. In this paper, we will review the data reporting the HLA-G involvement
of HLA-G in human organ transplantation, then factors that can modulate HLA-G, and finally the use of HLA-G as a therapeutic
tool in organ transplantation. 相似文献
6.
Kiave-Yune HoWangYin Maria Loustau Juan Wu Estibaliz Alegre Marina Daouya Julien Caumartin Sylvie Sousa Anatolij Horuzsko Edgardo D. Carosella Joel LeMaoult 《Cellular and molecular life sciences : CMLS》2012,69(23):4041-4049
The non-classical Human leukocyte antigen G (HLA-G) differs from classical HLA class I molecules by its low genetic diversity, a tissue-restricted expression, the existence of seven isoforms, and immuno-inhibitory functions. Most of the known functions of HLA-G concern the membrane-bound HLA-G1 and soluble HLA-G5 isoforms, which present the typical structure of classical HLA class I molecule: a heavy chain of three globular domains α1–α2–α3 non-covalently bound to β-2-microglobulin (B2M) and a peptide. Very little is known of the structural features and functions of other HLA-G isoforms or structural conformations other than B2M-associated HLA-G1 and HLA-G5. In the present work, we studied the capability of all isoforms to form homomultimers, and investigated whether they could bind to, and function through, the known HLA-G receptors LILRB1 and LILRB2. We report that all HLA-G isoforms may form homodimers, demonstrating for the first time the existence of HLA-G4 dimers. We also report that the HLA-G α1–α3 structure, which constitutes the extracellular part of HLA-G2 and HLA-G6, binds the LILRB2 receptor but not LILRB1. This is the first report of a receptor for a truncated HLA-G isoform. Following up on this finding, we show that the α1–α3-Fc structure coated on agarose beads is tolerogenic and capable of prolonging the survival of skin allografts in B6-mice and in a LILRB2-transgenic mouse model. This study is the first proof of concept that truncated HLA-G isoforms could be used as therapeutic agents. 相似文献
7.
Donadi EA Castelli EC Arnaiz-Villena A Roger M Rey D Moreau P 《Cellular and molecular life sciences : CMLS》2011,68(3):369-395
The HLA-G gene displays several peculiarities that are distinct from those of classical HLA class I genes. The unique structure of
the HLA-G molecule permits a restricted peptide presentation and allows the modulation of the cells of the immune system.
Although polymorphic sites may potentially influence all biological functions of HLA-G, those present at the promoter and
3′ untranslated regions have been particularly studied in experimental and pathological conditions. The relatively low polymorphism
observed in the MHC-G coding region both in humans and apes may represent a strong selective pressure for invariance, whereas,
in regulatory regions several lines of evidence support the role of balancing selection. Since HLA-G has immunomodulatory
properties, the understanding of gene regulation and the role of polymorphic sites on gene function may permit an individualized
approach for the future use of HLA-G for therapeutic purposes. 相似文献
8.
Lesport E Baudhuin J Sousa S LeMaoult J Zamborlini A Rouas-Freiss N Carosella ED Favier B 《Cellular and molecular life sciences : CMLS》2011,68(20):3385-3399
Vγ9Vδ2 T cells play a crucial role in the antitumoral immune response through cytokine production and cytotoxicity. Although
the expression of the immunomodulatory molecule HLA-G has been found in diverse tumors, its impact on Vγ9Vδ2 T-cell functions
remains unknown. Here we showed that soluble HLA-G inhibits Vγ9Vδ2 T-cell proliferation without inducing apoptosis. Moreover,
soluble HLA-G inhibited the Vγ9Vδ2 T-cell production of IFN-γ induced by phosphoantigen stimulation. The reduction in Vγ9Vδ2
T-cell IFN-γ production was also induced by membrane-bound or soluble HLA-G expressed by tumor cell lines. Finally, primary
tumor cells inhibited Vγ9Vδ2 T-cell proliferation and IFN-γ production through HLA-G. In this context, HLA-G impaired Vγ9Vδ2
T-cell cytotoxicity by interacting with ILT2 inhibitory receptor. These data demonstrate that HLA-G inhibits the anti-tumoral
functions of Vγ9Vδ2 T cells and imply that treatments targeting HLA-G could optimize Vγ9Vδ2 T-cell-mediated immunotherapy
of cancer. 相似文献
9.
Immunotolerant functions of HLA-G 总被引:9,自引:0,他引:9
Carosella ED Dausset J Rouas-Freiss N 《Cellular and molecular life sciences : CMLS》1999,55(3):327-333
10.
M. O'Brien T. McCarthy D. Jenkins P. Paul J. Dausset E.D. Carosella P. Moreau 《Cellular and molecular life sciences : CMLS》2001,58(12-13):1943-1949
11.
12.
Gömez-Casado E Martínez-Lasot J Castro MJ Morales P Trápaga J Berciano M Lowy E Arnaiz-Villena A 《Cellular and molecular life sciences : CMLS》1999,56(3-4):356-362
HLA-E and -G genes show a restricted polymorphism encoding for molecules whose variability is limited at the peptide binding
site. Fourteen alleles that give rise to only three productive proteins for HLA-G (*0101, *0103 and *0104) and five alleles
with three different proteins for HLA-E (*0101, *0102 and *0103) have been described. Expression of these molecules is low
and found in many tissues for HLA-E; HLA-G protein is expressed in extravillous trophoblast cells and thymic epithelium. Molecular
studies have shown how HLA-G and HLA-E bind to natural killer (NK) cells immunoglobulin and lectin-type inhibitory receptors.
HLA-E may act as a sentinel of the cell; if classical class I and HLA-G are being expressed, HLA-E molecules may reach the
cell surface and inhibit the lysis by NK cells. Most findings are consistent with the hypothesis that HLA-E and -G proteins
may be tolerogenic molecules at either the T-cell receptor (TcR) (inflammation, graft rejection) or NK level, switching off
cells which usually attack foreign (including foetus) or self (autoimmune) antigens. A low HLA-E and -G polymorphism is observed
in humans, and their allele frequencies are mostly homogeneous in the populations tested so far. Many studies to detect these
alleles are now being performed in isolated populations and also in pregnancy-associated pathologies. In the present paper,
standard and detailed techniques to detect HLA-E and -G DNA polymorphism are reported and discussed.
Received 14 July 1999; received after revision 25 August 1999; accepted 25 August 1999 相似文献
13.
The central nervous system (CNS) is considered an immune-privileged organ that maintains an adaptable immune surveillance
system. Dysregulated immune function within the CNS contributes to the development of brain tumor growth, and robust immune
activation results in excessive inflammation. Human lymphocyte antigen-G (HLA-G) proteins with tolerogenic immunoreactivity
have been implicated in various pathophysiological processes including immune surveillance, governing homeostasis and immune
regulation. In this review, we describe the wealth of evidence for the involvement of HLA-G in the CNS under physiological
and pathological conditions. Further, we review regulatory functions that may be applicable as beneficial strategies in the
therapeutic manipulation of immune-mediated CNS immune responses. Additionally, we try to understand how this molecule cooperates
with other CNS-resident cells to maintain normal immune homeostasis, while still facilitating the development of the appropriate
immune responses. 相似文献
14.
Emerging topics and new perspectives on HLA-G 总被引:1,自引:1,他引:0
Fainardi E Castellazzi M Stignani M Morandi F Sana G Gonzalez R Pistoia V Baricordi OR Sokal E Peña J 《Cellular and molecular life sciences : CMLS》2011,68(3):433-451
Following the Fifth International Conference on non-classical HLA-G antigens (HLA-G), held in Paris in July 2009, we selected
some topics which focus on emerging aspects in the setting of HLA-G functions. In particular, HLA-G molecules could play a
role in: (1) various inflammatory disorders, such as multiple sclerosis, intracerebral hemorrhage, gastrointestinal, skin
and rheumatic diseases, and asthma, where they may act as immunoregulatory factors; (2) the mechanisms to escape immune surveillance
utilized by several viruses, such as human cytomegalovirus, herpes simplex virus type 1, rabies virus, hepatitis C virus,
influenza virus type A and human immunodeficiency virus 1 (HIV-1); and (3) cytokine/chemokine network and stem cell transplantation,
since they seem to modulate cell migration by the downregulation of chemokine receptor expression and mesenchymal stem cell
activity blocking of effector cell functions and the generation of regulatory T cells. However, the immunomodulatory circuits
mediated by HLA-G proteins still remain to be clarified. 相似文献
15.
Stahn R Grittner C Zeisig R Karsten U Felix SB Wenzel K 《Cellular and molecular life sciences : CMLS》2001,58(1):141-147
E-selectin, exclusively expressed on activated endothelial cells, is a potential target for site-directed delivery of agents.
We and others have shown that sialyl Lewisx-liposomes (sLex-liposomes) are recognized by E-selectin. We now report an approach employing sLex-liposomes to deliver antisense oligonucleotides (AS-ODNs) directed against the adhesion molecule ICAM-1 to activated vascular
endothelial cells. ICAM-1 expression was analyzed at the protein level by immunofluorescence and a cell surface ELISA, and
at the RNA level by RT-PCR. We have investigated two different AS-ODNs complementary to the 3′ untranslated region and the
AUG translation initiation codon of ICAM-1 mRNA. Both inhibited protein expression, but did not influence the mRNA level,
pointing to a hybridization of AS-ODNs with the mRNA in the cytoplasm. Our results demonstrate the feasibility of a novel
approach for the delivery of agents to activated endothelial cells by glycoliposomes targeted to E-selectin.
Received 16 October 2000; revised 29 November 2000; accepted 29 November 2000 相似文献
16.
J Schwartz A Eyquem S Chaffaux 《Comptes rendus des séances de l'Académie des sciences. Série D, Sciences naturelles》1977,284(16):1561-1564
A peritoneal cell rich fluid, containing mononucleated leukocytes, macrophages, monocytes, mast cells and lymphocytes, was observed during normal pregnancy in animals belonging to various species. These cells might be concerned in a homograft-like, mother-foetus, relationship. 相似文献
17.
Born WK Zhang L Nakayama M Jin N Chain JL Huang Y Aydintug MK O'Brien RL 《Cellular and molecular life sciences : CMLS》2011,68(14):2335-2343
γδ T cells express adaptive antigen receptors encoded by rearranging genes. Their diversity is highest in the small region
of TCR V–J junctions, especially in the δ chain, which should enable the γδ TCRs to distinguish differences in small epitopes.
Indeed, recognition of small molecules, and of an epitope on a larger protein has been reported. Responses to small non-peptides
known as phospho-antigens are multi-clonal yet limited to a single γδ T cell subset in humans and non-human primates. Responses
to small peptides are multi-clonal or oligo-clonal, include more than one subset of γδ T cells, and occur in rodents and primates.
However, less effort has been devoted to investigate the peptide responses. To settle the questions of whether peptides can
be ligands for the γδ TCRs, and whether responses to small peptides might occur normally, peptide binding will have to be
demonstrated, and natural peptide ligands identified. 相似文献
18.
Siobhán C. Cowley 《Cellular and molecular life sciences : CMLS》2014,71(24):4831-4840
Mucosa-associated invariant T (MAIT) cells are a unique population of innate T cells that are abundant in humans. These cells possess an evolutionarily conserved invariant T cell receptor α chain restricted by the nonpolymorphic class Ib major histocompatibility (MHC) molecule, MHC class I-related protein (MR1). The recent discovery that MAIT cells are activated by MR1-bound riboflavin metabolite derivatives distinguishes MAIT cells from all other αβ T cells in the immune system. Since mammals lack the capacity to synthesize riboflavin, intermediates from the riboflavin biosynthetic pathway are distinct microbial molecular patterns that provide a unique signal to the immune system. Multiple lines of evidence suggest that MAIT cells, which produce important cytokines such as IFN-γ, TNF, and IL-17A, have the potential to influence immune responses to a broad range of pathogens. Here we will discuss our current understanding of MAIT cell biology and their role in pathogen defense. 相似文献
19.
Mattii L Bianchi F Pellegrini S Dolfi A Bernardini N 《Cellular and molecular life sciences : CMLS》2000,57(13-14):1990-1996
The small G protein Rho subfamily controls several cellular events such as growth, movement, proliferation and differentiation by rearranging actin and cytoskeleton proteins. Most of these effects are mediated by the activation of growth factor and extracellular matrix molecule receptors, suggesting a role for Rho molecules in the transduction pathway of these receptors. Despite the importance of Rho peptides in fundamental cellular events, data on their subcellular immunolocalisation are sparse: here we investigated the expression and subcellular localisation of RhoA in resting (cultured on plastic) and activated (Matri-cell or hepatocyte growth factor) MDCK cells by immunoperoxidase and immunogold techniques. Resting MDCK cells contain detectable amounts of RhoA mainly localised in the cytoplasm; RhoA expression is significantly enhanced by Matri-cell substrates that promote translocation of RhoA at the membrane level. This enhancing effect is reduced after exposure to hepatocyte growth factor. 相似文献
20.
The steel factor (SLF) and c-Kit growth factor/receptor pair are key molecules governing mast cell development and survival. SLF is expressed on stromal cells as a membrane-bound molecule (mSLF) which can be cleaved by proteases to release a soluble form (sSLF). We investigated the importance of phospholipase C (PLC) activation in mast cells stimulated by sSLF and mSLF. PLC antagonists U73122, neomycin sulfate and oleic acid inhibited mast cell thymidine incorporation stimulated by mSLF, but not by sSLF. These antagonists suppressed sSLF-induced Ca2+ transients but did not significantly interfere with c-Kit phosphorylation or PLC-gamma2 recruitment. p85, the regulatory subunit of phosphatidylinositol 3-kinase (PI3-kinase), was found to be efficiently recruited to c-Kit following stimulation by sSLF or mSLF. However PKB/Akt, a kinase activated by PI3-kinase products, was phosphorylated following sSLF stimulation, but not with mSLF. Taken together, these studies demonstrate the importance of PLC activation by mSLF in supporting mast cells. 相似文献