Isoforms of human leukocyte antigen-G and their inhibitory receptors in human kidney allograft acceptance

Wu, Juan; Zhang, Wei; Hernandez-Lopez, Pedro; Fabelo, Edward; Parikh, Mehul; Mulloy, Laura L.; Horuzsko, Anatolij

doi:10.1016/j.humimm.2009.07.023

Cited by 10 publications

(6 citation statements)

References 63 publications

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“…Since the discovery in the 1990s that HLA-G played a relevant physiological role in the induction of maternal-fetal tolerance, the idea of investigating the role of HLA-G in allografting has taken hold. Several studies have been reported demonstrating that the presence of HLA-G in the allograft [155–158] or the increase of soluble HLA-G serum/plasma levels [159–166] are associated with better graft acceptance, increased graft survival or both.…”

Section: Hla-g Polymorphism and Disease Associationsmentioning

confidence: 99%

Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association

Donadi

Castelli

Arnaiz‐Villena³

et al. 2010

Cell. Mol. Life Sci.

318

405

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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.

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Section: Hla-g Polymorphism and Disease Associationsmentioning

confidence: 99%

Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association

Donadi

Castelli

Arnaiz‐Villena³

et al. 2010

Cell. Mol. Life Sci.

318

405

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“…Indeed, proinflammatory cytokines and T cell activation can be expected after recognition of donor HLA antigens, either by the direct pathway (donor HLA on donor antigen-presenting cells), the semidirect pathway (intact donor HLA on recipient’s antigen-presenting cells), or by the indirect pathway (self-restricted presentation of processed donor-derived HLA HCs on HLA molecules on recipient antigen-presenting cells) [ 138 ]. In this regard, Horuzko’s team of investigators [ 139 , 140 , 141 , 142 ] have observed HLA-G with a high level of HLA-G dimers in circulation and augmented expression of the membrane-bound HLA-G on monocytes which are associated with the prolongation of kidney allograft survival. Interestingly, the HLA-G dimer in circulation was higher in a group of 90 patients with a functioning allograft compared with 40 patients who underwent allograft rejection.…”

Section: Current Concepts Concerning Oligomerization Of Face-2mentioning

confidence: 99%

“…The binding of these mAbs, and particularly that of MEM-E/02, was selectively inhibited by two peptides commonly shared by almost all HLA loci. They are 115 QFAYDGKDY 123 (present in all alleles of HLA-A, -B, -C, -E, -F, and -G loci) and 137 DTAAQI 142 (present in HLA-B and HLA-C) [32] (Figure 3). Further inhibition experiments carried out with the peptide sequences on the binding of mAbs MEM-E02, E07, and E08 to HCs of different HLA loci coated on solid matrix (LABScreen beadsets) revealed the sequences ( 115 QFAYDGKDY 123 and 137 DTAAQI 142 ) and inhibited the binding of the mAbs in a dosimetric manner (Figure 3A-C in [37]).…”

Section: Hla-iamentioning

confidence: 99%

Cell Surface B2m-Free Human Leukocyte Antigen (HLA) Monomers and Dimers: Are They Neo-HLA Class and Proto-HLA?

Ravindranath

Selvan

et al. 2023

Biomolecules

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Cell surface HLA-I molecules (Face-1) consist of a polypeptide heavy chain (HC) with two groove domains (G domain) and one constant domain (C-domain) as well as a light chain, B2-microglobulin (B2m). However, HCs can also independently emerge unfolded on the cell surface without peptides as B2m-free HC monomers (Face-2), B2m-free HC homodimers (Face 3), and B2m-free HC heterodimers (Face-4). The transport of these HLA variants from ER to the cell surface was confirmed by antiviral antibiotics that arrest the release of newly synthesized proteins from the ER. Face-2 occurs at low levels on the normal cell surface of the lung, bronchi, epidermis, esophagus, breast, stomach, ilium, colorectum, gall bladder, urinary bladder, seminal vesicles ovarian epithelia, endometrium, thymus, spleen, and lymphocytes. They are upregulated on immune cells upon activation by proinflammatory cytokines, anti-CD3 antibodies, antibiotics (e.g., ionomycin), phytohemagglutinin, retinoic acid, and phorbol myristate acetate. Their density on the cell surface remains high as long as the cells remain in an activated state. After activation-induced upregulation, the Face-2 molecules undergo homo- and hetero-dimerization (Face-3 and Face-4). Alterations in the redox environment promote dimerization. Heterodimerization can occur among and between the alleles of different haplotypes. The glycosylation of these variants differ from that of Face-1, and they may occur with bound exogenous peptides. Spontaneous arthritis occurs in HLA-B27+ mice lacking B2m (HLA-B27+ B2m−/−) but not in HLA-B27+ B2m+/− mice. The mice with HLA-B27 in Face-2 spontaneous configuration develop symptoms such as changes in nails and joints, hair loss, and swelling in paws, leading to ankyloses. Anti-HC-specific mAbs delay disease development. Some HLA-I polyreactive mAbs (MEM series) used for immunostaining confirm the existence of B2m-free variants in several cancer cells. The upregulation of Face-2 in human cancers occurs concomitantly with the downregulation of intact HLAs (Face-1). The HLA monomeric and dimeric variants interact with inhibitory and activating ligands (e.g., KIR), growth factors, cytokines, and neurotransmitters. Similarities in the amino acid sequences of the HLA-I variants and HLA-II β-chain suggest that Face-2 could be the progenitor of both HLA classes. These findings may support the recognition of these variants as a neo-HLA class and proto-HLA.

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“…The tolerogenic functions of HLA-G1 and HLA-G5 are highly dependent on their form (monomer or dimer) [130]. HLA-G is expressed in disulfide-linked dimer form at the cell surface [131], and, to lesser extent, in solution [132].…”

Section: Hla-g-induced Tr Cellsmentioning

confidence: 99%

The role of HLA-G in immunity and hematopoiesis

Carosella

Gregori

Rouas‐Freiss

et al. 2010

Cell. Mol. Life Sci.

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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.

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Isoforms of human leukocyte antigen-G and their inhibitory receptors in human kidney allograft acceptance

Cited by 10 publications

References 63 publications

Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association

Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association

Cell Surface B2m-Free Human Leukocyte Antigen (HLA) Monomers and Dimers: Are They Neo-HLA Class and Proto-HLA?

The role of HLA-G in immunity and hematopoiesis

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