Expression of classical <scp>HLA</scp> class I molecules: regulation and clinical impacts

René, Céline; Lozano, Claire; Eliaou, Jean‐François

doi:10.1111/tan.12787

Cited by 25 publications

(26 citation statements)

References 106 publications

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“…The products of these alleles have different immunological functions based on their ability to present specific peptides to cytotoxic T lymphocytes and bind various KIR ligands on NK cells, and their expression levels can extensively affect biological and pathological processes. 1 It has been confirmed that the expression levels of different alleles on the same HLA class I locus can vary dramatically. [2][3][4][5][6] This differential HLA expression according to alleles could have a broad clinical impact, such as influencing virus infection control, 4,7 risk of autoimmune disorders, 4,[8][9][10] and haematopoietic stem cell transplantation (HSCT) outcomes.…”

Section: Introductionmentioning

confidence: 95%

“…More than 10 000 alleles on HLA‐A, ‐B, and ‐C loci have been revealed in human populations. The products of these alleles have different immunological functions based on their ability to present specific peptides to cytotoxic T lymphocytes and bind various KIR ligands on NK cells, and their expression levels can extensively affect biological and pathological processes …”

Section: Introductionmentioning

confidence: 99%

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Quantification of classical HLA class I mRNA by allele‐specific, real‐time polymerase chain reaction for most Han individuals

Pan

Lü

et al. 2017

HLA

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Recent studies have shown that expression levels of different alleles at the same HLA class I locus can vary dramatically, which might have a broad influence on human disease. However, precise quantification of the relative expression level of each HLA allele is challenging, because distinguishing different alleles on the same locus is difficult. Here, we developed a series of allele-specific, real-time polymerase chain reaction assays for quantifying HLA class I allele mRNA in most Han individuals. The alleles of almost all heterozygous genotypes with a frequency higher than 0.5% in our population (78 alleles on HLA-A locus, 124 alleles on HLA-B locus, and 74 alleles on HLA-C locus) were specifically amplified. The specificity of the amplification was strictly validated by setting the corresponding negative control for each allele of each genotype. The amplification efficiency of each reaction was determined, and the slopes of the reactions were compared. This study provides a tool for detecting the comprehensive expression profile of HLA class I alleles and will be useful not only for the investigation of the molecular mechanism underlying HLA allele expression regulation but also for exploration of immunological mechanisms involving HLA expression in the fields of tumour immune evasion, viral infection, auto-immune disorders, and graft vs host disease after haematopoietic stem cell transplantation.

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Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Quantification of classical HLA class I mRNA by allele‐specific, real‐time polymerase chain reaction for most Han individuals

Pan

Lü

et al. 2017

HLA

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“…It must be emphasized that the regulation of MHC class I gene expression by these hormones and growth factors involves the binding of NF-κB dimers to the enhancer A region of the MHC class I promoter (Figure 2 ). The enhancer A region is located in a “hormone-sensitive region” of the MHC class I promoter (i.e., −500 to −68 bp), and this region is responsible for the regulation of MHC class I expression by hormones, cytokines, chemokines, and drugs ( 33 , 35 , 40 ). The enhancer A sequence (5′-GGGGAGTCCCC-3′) that spans nucleotides −180 bp to −170 bp is a palindromic variant of the κB consensus site, and it can bind NF-κB dimers ( 43 ).…”

Section: Nf-κb and The Thyroidmentioning

confidence: 99%

The Role of the Transcription Factor Nuclear Factor-kappa B in Thyroid Autoimmunity and Cancer

2018

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Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor that is involved in inflammatory and immune responses, as well as in regulation of expression of many other genes related to cell survival, proliferation, and differentiation. In mammals, NF-κB comprises five subunits that can bind to promoter regions of target genes as homodimers or heterodimers. The most common dimer is the p50/p65 heterodimer. The several combinations of dimers that can be formed contribute to the heterogeneous regulation of NF-κB target genes, and this heterogeneity is further increased by interactions of the NF-κB dimers with other transcription factors, such as steroid hormone receptors, activator protein-1 (AP-1), and cAMP response element binding protein (CREB). In the thyroid, several studies have demonstrated the involvement of NF-κB in thyroid autoimmunity, thyroid cancer, and thyroid-specific gene regulation. The role of NF-κB in thyroid autoimmunity was hypothesized more than 20 years ago, after the finding that the binding of distinct NF-κB heterodimers to the major histocompatibility complex class I gene is hormonally regulated. Further studies have shown increased activity of NF-κB in thyroid autoimmune diseases and in thyroid orbitopathy. Increased activity of NF-κB has also been observed in thyroid cancer, where it correlates with a more aggressive pattern. Of particular interest, mutation of some oncogenes or tumor suppressor genes involved in thyroid carcinogenesis results in constitutive activation of the NF-κB pathway. More recently, it has been shown that NF-κB also has a role in thyroid physiology, as it is fundamental for the expression of the main thyroid-specific genes, such as sodium iodide symporter, thyroid peroxidase, thyroglobulin, Pax8, and TTF-1 (NKX2-1).

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“…HLA expression is also impacted by 5 ′ and 3 ′ UTR containing, e.g. promoter and microRNA binding sites (12)(13)(14). Variation in these sites has been observed, e.g.…”

Section: Introductionmentioning

confidence: 99%

Limited HLA sequence variation outside of antigen recognition domain exons of 360 10 of 10 matched unrelated hematopoietic stem cell transplant donor‐recipient pairs

Hou

Vierra-Green

Lázaro

et al. 2016

HLA

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Traditional DNA-based typing focuses primarily on interrogating the exons of HLA genes that form the antigen recognition domain (ARD). The relevance of mismatching donor and recipient for HLA variation outside the ARD on hematopoietic stem cell transplantation (HCT) outcomes is unknown. This study was designed to evaluate the frequency of variation outside the ARD in 10/10 (HLA-A, -B, -C, -DRB1, -DQB1) matched unrelated donor transplant pairs (n=360). Next generation DNA sequencing was used to characterize both HLA exons and introns for HLA-A, -B, -C alleles; exons 2, 3 and the intervening intron for HLA-DRB1; and exons only for HLA-DQA1 and -DQB1. Over 97% of alleles at each locus were matched for their nucleotide sequence outside of the ARD exons. Of the 4320 allele comparisons overall, only 17 allele pairs were mismatched for non-ARD exons, 41 for noncoding regions and 9 for ARD exons. The observed variation between donor and recipient usually involved a single nucleotide difference (88% of mismatches); 88% of the non-ARD exon variants impacted the amino acid sequence. The impact of amino acid sequence variation caused by substitutions in exons outside ARD regions in D-R pairs will be difficult to assess in HCT outcome studies since these mismatches do not occur very frequently.

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Expression of classical HLA class I molecules: regulation and clinical impacts

Cited by 25 publications

References 106 publications

Quantification of classical HLA class I mRNA by allele‐specific, real‐time polymerase chain reaction for most Han individuals

Quantification of classical HLA class I mRNA by allele‐specific, real‐time polymerase chain reaction for most Han individuals

The Role of the Transcription Factor Nuclear Factor-kappa B in Thyroid Autoimmunity and Cancer

Limited HLA sequence variation outside of antigen recognition domain exons of 360 10 of 10 matched unrelated hematopoietic stem cell transplant donor‐recipient pairs

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