The Class I HLA Repertoire of Pancreatic Islets Comprises the Nonclassical Class Ib Antigen HLA-G

Cirulli, Vincenzo; Zalatan, Jessie; McMaster, Michael; Prinsen, Robyn; Salomon, Daniel R.; Ricordi, Camillo; Torbett, Bruce E.; Meda, Paolo; Crisá, Laura

doi:10.2337/db05-0731

Cited by 144 publications

(105 citation statements)

References 37 publications

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“…23,24 More importantly, a recent report demonstrated constitutive expression of HLA-G in pancreatic islets and suggested an immunoregulatory role with possible implications for autoimmunity. 25 Unlike the classical MHC class I genes, the non-classical genes exhibit low polymorphy in the coding regions. Therefore, these results suggest that fine mapping of the HLA-G gene, with the surrounding region to include putative regulatory sites, is warranted in T1D.…”

Section: Discussionmentioning

confidence: 99%

Conditional analyses on the T1DGC MHC dataset: novel associations with type 1 diabetes around HLA-G and confirmation of HLA-B

et al. 2008

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The major histocompatibility complex (MHC) is known to harbour genetic risk factors for type 1 diabetes (T1D) additional to the class II determinants HLA-DRB1, -DQA1 and -DQB1, but strong linkage disequilibrium (LD) has made efforts to establish their location difficult. This study utilizes a dataset generated by the T1D genetics consortium (T1DGC), with genotypes for 2965 markers across the MHC in 2321 T1D families of multiple (mostly Caucasian) ethnicities. Using a comprehensive approach consisting of complementary conditional methods and LD analyses, we identified three regions with T1D association, independent both of the known class II determinants and of each other. A subset of polymorphisms that could explain most of the association in each region included single nucleotide polymorphisms (SNPs) in the vicinity of HLA-G, particular HLA-B and HLA-DPB1 alleles, and SNPs close to the COL11A2 and RING1 genes. Apart from HLA-B and HLA-DPB1, all of these represent novel associations, and subpopulation analyses did not indicate large population-specific differences among Caucasians for our findings. On account of the unusual genetic complexity of the MHC, further fine mapping is demanded, with the possible exception of HLA-B. However, our results mean that these efforts can be focused on narrow, defined regions of the MHC.

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Section: Discussionmentioning

confidence: 99%

Conditional analyses on the T1DGC MHC dataset: novel associations with type 1 diabetes around HLA-G and confirmation of HLA-B

et al. 2008

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“…In physiological conditions, HLA-G expression was also found in erythroid precursors, cornea, thymic medulla and pancreatic islets (8,(9)(10)(11). However, HLA-G can be neoexpressed in pathological conditions including cancers, transplantation, and inflammatory and autoimmune diseases and viral infections (3,5,12,13).…”

Section: Mechanisms Of Hla-g Involved In Tumor Immunologymentioning

confidence: 99%

Human Leukocyte Antigen-G (HLA-G) Expression in Cancers: Roles in Immune Evasion, Metastasis and Target for Therapy

Lin

Yan

2015

Mol Med

109

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Aberrant induction of human leukocyte antigen-G (HLA-G) expression has been observed in various malignancies and is strongly associated with tumor immune escape, metastasis and poor prognosis. To date, great achievements have been made in understanding the underlying mechanisms of HLA-G involved in tumor progression. HLA-G could lead to tumor evasion by inhibition of immune cell cytolysis, differentiation and proliferation and inhibition of cytokine production, induction of immune cell apoptosis, generation of regulatory cells and expansion of myeloid-derived suppressive cells and by impairment of chemotaxis. Moreover, HLA-G could arm tumor cells with a higher invasive and metastatic potential with the upregulation of tumor-promoting factor expression such as matrix metalloproteinases (MMPs), indicating that ectopic HLA-G expression could render multiple effects during the progression of malignancies. In this review, we summarized the mechanisms of HLA-G involved in promoting tumor cell immune escaping, metastasis and disease progression. Special attention will be paid to its significance as an attractive therapeutic target in cancers.

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“…HLA-G is detected in a few fetal tissues, which include cytotrophoblasts and amnion of the placenta (9,10) and a few healthy adult tissues, including thymus (11), cornea (12), pancreas (13), and erythroblasts (14). Nonetheless, because all HLA-I molecules share 80% amino acid, cross-reactivity to the other HLA by HLA-G Abs has been hypothesized for studies in which biochemical analysis to identify the 39-kD H chain of HLA-G was not done.…”

Section: Rreb-1 Is a Transcriptionalmentioning

confidence: 99%

RREB-1 Is a Transcriptional Repressor of HLA-G

Flajollet

Poras

Carosella

et al. 2009

The Journal of Immunology

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The nonclassical HLA-G is a molecule specifically involved in immune tolerance with highly restricted tissue distribution in healthy conditions. Yet it is overexpressed in numerous tumors and in allografts with better acceptance. Major mechanisms involved in regulation of HLA-G transcription are still poorly described. Thus, to characterize these mechanisms we have developed a specific proteomic approach to identify proteins that bind differentially to the HLA-G gene promoter by promoter pull-down assay followed by spectrometry mass analysis. Among specific binding factors, we focused on RREB-1, a ras-responsive element binding protein 1. We demonstrated that RREB-1 represses HLA-G transcriptional activity and binds three ras response elements within the HLA-G promoter. RREB-1 protein, specifically in HLA-G-negative cells, interacts with subunits of CtBP complex implicated in chromatin remodeling. This demonstration is the first of a repressor factor of HLA-G transcriptional activity taking part in HLA-G repression by epigenetic mechanisms.

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The Class I HLA Repertoire of Pancreatic Islets Comprises the Nonclassical Class Ib Antigen HLA-G

Cited by 144 publications

References 37 publications

Conditional analyses on the T1DGC MHC dataset: novel associations with type 1 diabetes around HLA-G and confirmation of HLA-B

Conditional analyses on the T1DGC MHC dataset: novel associations with type 1 diabetes around HLA-G and confirmation of HLA-B

Human Leukocyte Antigen-G (HLA-G) Expression in Cancers: Roles in Immune Evasion, Metastasis and Target for Therapy

RREB-1 Is a Transcriptional Repressor of HLA-G

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