<scp>HLA</scp>‐G 5′ <scp>URR SNP</scp>s and 3′ <scp>UTR</scp> 14‐bp insertion/deletion polymorphism in an <scp>A</scp>fro‐<scp>B</scp>razilian population from <scp>P</scp>araná <scp>S</scp>tate

Tureck, Luciane Viater; Santos, Luana Carvalho dos; Wowk, Pryscilla Fanini; Mattar, S. B.; Silva, J. S.; Magalhães, Justino; Roxo, Valéria Maria Munhoz Sperandio; Bicalho, Maria Gabriela Parenti

doi:10.1111/iji.12068

Cited by 4 publications

(1 citation statement)

References 38 publications

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“…At present there are 82 different HLA-G alleles in the IPD-IMGT/HLA database (3.44.0), encoding 22 different proteins, whereas 4 null alleles have been identified. Due to a rather conserved molecule more attention has been paid to analysis of the promotor region (5' upstream regulatory region, 5' URR) and the 3' UTR region that are thought to play a role in the expression levels of HLA-G and thus influence its immunotolerogenic (or immunomodulatory) properties (173,(222)(223)(224)(225)(226). Especially the 14 bp insertion/deletion that was identified in the 3' UTR region and correlated with mRNA stability and thus expression levels has been intensively studied by different methods, ranging from real time TaqMan PCR (227), amplification of part of the 3' UTR region followed by size discrimination analyzed by gel electrophoresis (228)(229)(230) to sequencing of this 3' UTR region (231)(232)(233).…”

Section: Non-classical Hla Class I Determinationmentioning

confidence: 99%

HLA Class I Molecules as Immune Checkpoints for NK Cell Alloreactivity and Anti-Viral Immunity in Kidney Transplantation

et al. 2021

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Natural killer (NK) cells are innate lymphocytes that can kill diseased- or virally-infected cells, mediate antibody dependent cytotoxicity and produce type I immune-associated cytokines upon activation. NK cells also contribute to the allo-immune response upon kidney transplantation either by promoting allograft rejection through lysis of cells of the transplanted organ or by promoting alloreactive T cells. In addition, they protect against viral infections upon transplantation which may be especially relevant in patients receiving high dose immune suppression. NK cell activation is tightly regulated through the integrated balance of signaling via inhibitory- and activating receptors. HLA class I molecules are critical regulators of NK cell activation through the interaction with inhibitory- as well as activating NK cell receptors, hence, HLA molecules act as critical immune checkpoints for NK cells. In the current review, we evaluate how NK cell alloreactivity and anti-viral immunity are regulated by NK cell receptors belonging to the KIR family and interacting with classical HLA class I molecules, or by NKG2A/C and LILRB1/KIR2DL4 engaging non-classical HLA-E or -G. In addition, we provide an overview of the methods to determine genetic variation in these receptors and their HLA ligands.

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Section: Non-classical Hla Class I Determinationmentioning

confidence: 99%

HLA Class I Molecules as Immune Checkpoints for NK Cell Alloreactivity and Anti-Viral Immunity in Kidney Transplantation

et al. 2021

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The association between the HLA-G 14-bp insertion/deletion polymorphism and type 1 diabetes

et al. 2015

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Type 1 diabetes (T1D) is a multifactorial disease that has a strong genetic component. The HLA-G is a nonclassical HLA class I locus that is associated with immunomodulatory functions, including downregulation of innate and adaptive immune responses and induction of immune tolerance. However, there is currently limited information about the involvement of HLA-G in T1D susceptibility. This case-control study aims to investigate the T1D susceptibility association of alleles and genotypes of a widely investigated 14-bp insertion/deletion polymorphism in the HLA-G and to provide further evidence of the frequency distribution of class II HLA-DR-DQ-risk genotypes in T1D children and adolescents in the Brazilian population. The deletion allele and the homozygous deletion genotype are associated with susceptibility to T1D and the insertion allele and the heterozygous deletion/insertion genotype are associated with protection from T1D. We also confirm that genetic susceptibility to T1D is associated with the DRB1*03:01-DQA1*05:01-DQB1*02:01 and DRB1*04-DQA1*03:01-DQB1*03:02 haplotypes in Brazilian northeast region. The DR3-DQ2/DR4-DQ8 genotype conferred the highest detected risk for T1D. Our results identify a novel association of the 14-bp deletion allele and the homozygous deletion genotype with T1D development and provide additional evidence of the importance of HLA class II heterozygous DR3-DQ2/DR4-DQ8 genotype in T1D susceptibility.

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Transcriptional and Posttranscriptional Regulations of theHLA-GGene

Castelli

Veiga‐Castelli

Yaghi

et al. 2014

Journal of Immunology Research

147

180

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HLA-G has a relevant role in immune response regulation. The overall structure of the HLA-G coding region has been maintained during the evolution process, in which most of its variable sites are synonymous mutations or coincide with introns, preserving major functional HLA-G properties. The HLA-G promoter region is different from the classical class I promoters, mainly because (i) it lacks regulatory responsive elements for IFN-γ and NF-κB, (ii) the proximal promoter region (within 200 bases from the first translated ATG) does not mediate transactivation by the principal HLA class I transactivation mechanisms, and (iii) the presence of identified alternative regulatory elements (heat shock, progesterone and hypoxia-responsive elements) and unidentified responsive elements for IL-10, glucocorticoids, and other transcription factors is evident. At least three variable sites in the 3′ untranslated region have been studied that may influence HLA-G expression by modifying mRNA stability or microRNA binding sites, including the 14-base pair insertion/deletion, +3142C/G and +3187A/G polymorphisms. Other polymorphic sites have been described, but there are no functional studies on them. The HLA-G coding region polymorphisms might influence isoform production and at least two null alleles with premature stop codons have been described. We reviewed the structure of the HLA-G promoter region and its implication in transcriptional gene control, the structure of the HLA-G 3′UTR and the major actors of the posttranscriptional gene control, and, finally, the presence of regulatory elements in the coding region.

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HLA‐G 5′ URR SNPs and 3′ UTR 14‐bp insertion/deletion polymorphism in an Afro‐Brazilian population from Paraná State

Cited by 4 publications

References 38 publications

HLA Class I Molecules as Immune Checkpoints for NK Cell Alloreactivity and Anti-Viral Immunity in Kidney Transplantation

HLA Class I Molecules as Immune Checkpoints for NK Cell Alloreactivity and Anti-Viral Immunity in Kidney Transplantation

The association between the HLA-G 14-bp insertion/deletion polymorphism and type 1 diabetes

Transcriptional and Posttranscriptional Regulations of theHLA-GGene

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