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The subversion mechanisms employed by Helicobacter pylori ( H. pylori) to escape from immune surveillance and to establish persistent infection are poorly understood. Growing evidence indicates that expression of HLA-G, a non-classical major histocompatibility complex molecule, negatively regulates immune responses in pathological conditions, including infectious diseases. In this context, we aimed to evaluate HLA-G expression in the gastric microenvironment of individuals harbouring H. pylori and to correlate it with histological variables. Fifty-four gastric specimens from patients harbouring H. pylori infection were evaluated by immunohistochemistry using anti- HLA-G monoclonal antibody. As a result, HLA-G expression was detected in 43 of 54 specimens harbouring H. pylori. The presence of HLA-G was significantly associated with milder colonization by H. pylori ( P < 0.02), milder inflammatory activity ( P < 0.02) and bacterium histological location in the gastric antrum. This study is the first to explore HLA-G expression in the context of bacterial infection. Whether the biological role of HLA-G during H. pylori infection is beneficial or hazardous for patients remains to be defined. [ABSTRACT FROM AUTHOR]

Human leukocyte antigen-G (HLA-G) has well-recognized immunosuppressive properties modulating the activity of many immune system cells, and polymorphisms observed at the HLA-G 5′ upstream regulatory region (5′URR) may influence gene transcriptional regulation. In this study, we characterized the sequence variation and haplotype structure of the HLA-G 5′URR in worldwide populations to investigate the evolutionary history of the HLA-G promoter and shed some light into the mechanisms that may underlie HLA-G expression control. A 1.4-kb region, encompassing the known HLA-G regulatory elements, was sequenced in three African populations from Senegal, Benin and Congo, and data were combined with those available in the literature, resulting in a total of 1411 individuals from 21 worldwide populations. High levels of nucleotide and haplotype diversities, excess of intermediate-frequency variants and reduced population differentiation were observed at this locus when compared with the background genomic variation. These features support a strong molecular signature of balancing selection at HLA-G 5′URR, probably as a result of the competing needs to maintain both a maternal-fetal immune tolerance and an efficient host immune response to invading pathogens during human evolution. An extended analysis of a 300-kb region surrounding HLA-G revealed that this region is not involved in a hitchhiking effect and may be the direct target of selection. [ABSTRACT FROM AUTHOR]

The HLA-G (human leukocyte antigen-G) molecule plays a pivotal role in immune tolerance by inhibiting different cell subsets involved in both innate and adaptive immunity. Besides its primary function in maintaining the maternal-fetal tolerance, HLA-G has been involved in a wide range of pathological conditions where it can be either favorable or detrimental to the patient, depending on the nature of the pathology. Although several studies have demonstrated the utmost importance of the 3′ untranslated region (3′UTR) in the HLA-G expression profile, limited data exist on the sequence variability of this gene region in human populations. In this study, we characterized the genetic diversity and haplotype structure of the HLA-G 3′UTR by resequencing 444 individuals from three sub-Saharan African populations and retrieving data from the 1000 Genomes project and the literature. A total of 1936 individuals representing 21 worldwide populations were combined and jointly analyzed. Our data revealed a high level of nucleotide diversity, an excess of intermediate frequency variants and an extremely low population differentiation, strongly supporting a history of balancing selection at this locus. The 14-bp insertion/deletion polymorphism was further pointed out as the likely target of selection, emphasizing its potential role in the post-transcriptional regulation of HLA-G expression. [ABSTRACT FROM AUTHOR]

The human leukocyte antigen-E ( HLA-E) locus is a human major histocompatibility complex ( MHC) gene associated with immune-modulation and suppression of the immune response by the interaction with specific natural killer ( NK) and T cell receptors (TCRs). It is considered one of the most conserved genes of the human MHC; however, this low nucleotide variability seems to be a consequence of the scarce number of studies focusing on this subject. In this manuscript we assessed the nucleotide variability at the HLA-E coding and 3′ untranslated regions (3′UTRs) in Brazil and in the populations from the 1000Genomes Consortium. Twenty-eight variable sites arranged into 33 haplotypes were detected and most of these haplotypes (98.2%) are encoding one of the two HLA-E molecules found worldwide, E*01:01 and E*01:03. Moreover, three worldwide spread haplotypes, associated with the coding alleles E*01:01:01, E*01:03:01 and E*01:03:02, account for 85% of all HLA-E haplotypes, suggesting that they arose early before human speciation. In addition, the low nucleotide diversity found for the HLA-E coding and 3′ UTR in worldwide populations suggests that the HLA-E gene is in fact a conserved gene, which might be a consequence of its key role in the modulation of the immune system. [ABSTRACT FROM AUTHOR]

Host and Plasmodium interactions result in highly variable clinical phenotypes, partly explained by the nature and level of anti-malarial antibody response. Human leukocyte antigen ( HLA)-G can create a tolerogenic environment, allowing parasites to escape from anti-malarial immunity. We performed a family-based association study encompassing 483 Sereer individuals (261 children and their parents), and reported two independent signals at the HLA-G 3′ untranslated region associated with antibody response to specific Plasmodium falciparum blood stage antigens, previously associated with malaria protection: (i) + 3010G together with + 3142C with total IgG and IgG1 against GLURP and (ii) + 3196G with IgG3 against MSP2. While these results require further investigation, they suggest for the first time a role of HLA-G in the regulation of humoral immune response in malaria. [ABSTRACT FROM AUTHOR]

The non-classical human leukocyte antigen (HLA) class I genes present a very low rate of variation. So far, only 10 HLA-E alleles encoding three proteins have been described, but only two are frequently found in worldwide populations. Because of its historical background, Brazilians are very suitable for population genetic studies. Therefore, 104 bone marrow donors from Brazil were evaluated for HLA-E exons 1-4. Seven variation sites were found, including two known single nucleotide polymorphisms (SNPs) at positions +424 and +756 and five new SNPs at positions +170 (intron 1), +1294 (intron 3), +1625, +1645 and +1857 (exon 4). Haplotyping analysis did show eight haplotypes, three of them known as E*01:01:01, E*01:03:01 and E*01:03:02:01 and five HLA-E new alleles that carry the new variation sites. The HLA-E*01:01:01 allele was the predominant haplotype (62.50%), followed by E*01:03:02:01 (24.52%). Selective neutrality tests have disclosed an interesting pattern of selective pressures in which balancing selection is probably shaping allele frequency distributions at an SNP at exon 3 (codon 107), sequence diversity at exon 4 and the non-coding regions is facing significant purifying pressure. Even in an admixed population such as the Brazilian one, the HLA-E locus is very conserved, presenting few polymorphic SNPs in the coding region. [ABSTRACT FROM AUTHOR]

As the mechanisms leading to the persistence of hepatitis B virus (HBV) infection are poorly understood and as the histocompatibility leucocyte antigen (HLA)-G is well described as a tolerogenic molecule, we evaluated HLA-G expression in 74 specimens of HBV liver biopsies and in 10 specimens obtained from previously healthy cadaver liver donors. HBV specimens were reviewed and classified by the METAVIR score, and HLA-G expression was assessed by immunohistochemistry. No HLA-G expression was observed in control hepatocytes. In contrast, 57 (77%) of 74 HBV specimens showed soluble and membrane-bound HLA-G expression in hepatocytes, biliary epithelial cells or both. No associations between the intensity of HLA-G expression and patient age or gender, HBeAg status, severity of liver fibrosis, and grade of histological findings were observed. Although significance was not reached ( P = 0.180), patients exhibiting HLA-G expression presented a higher median HBV DNA viral load (10 copies/mL) than those who did not express HLA-G (10 copies/mL). These results indicate that HLA-G is expressed in most cases of chronic HBV infection in all stages and may play a role in the persistency of HBV infection. [ABSTRACT FROM AUTHOR]

The human leukocyte antigen (HLA)-G non-classical major histocompatibility complex (MHC) class I molecule was originally described in first-trimester trophoblasts at the fetal–maternal interface in 1990. Eight years later, the First International Conference on this molecule was inaugurated by Prof Jean Dausset, recipient of the Nobel Prize in Medicine. The Fifth International Conference on HLA-G, held in Paris on July 2009, began with a tribute to Prof Jean Dausset who left us recently. This conference was co-chaired by Dr Edgardo D. Carosella and Prof Hans Grosse-Wilde, included 57 oral presentations and was attended by approximately 140 delegates from 16 countries. We summarize here the major advances on the HLA-G molecule that were reported, including findings on its biological activity and characterization of new mechanisms of action, notably through mesenchymal stem cells and regulatory cells, and the previously unexplored role of HLA-G on immune cells such as γδ T-cells and B lymphocytes. Furthermore, the role of HLA-G during pregnancy was revisited and its impact in pathologies such as cancer, autoimmune disorders and transplantation was further extended. [ABSTRACT FROM AUTHOR]

Human leukocyte antigen (HLA)-G is a nonclassical HLA class I molecule from the major histocompatibility complex, which was initially shown to confer protection to the fetus from her mother’s immune system. The Third International Conference on HLA-G, held in 2003, showed that beyond its role in fetal–maternal tolerance, HLA-G exerts tolerogenic functions involved in transplant acceptance as well as in tumoral and viral immune escape. The Fourth International Conference, which took place in Paris on July 2006, counted 72 oral presentations and about 200 attendees from 25 countries. The reports presented brought new insight into HLA-G research, and we summarize here the major advances on the HLA-G biology that were reported. Abstracts for all presentations can be found in volume 68 issue number 4 of Tissue Antigens. [ABSTRACT FROM AUTHOR]

The HLA-G molecule plays a crucial role in the protection of the fetus against aggression by the mother’s immune system. Recently, it was shown that HLA-G was involved in the protection of the transplanted tissues, via the inhibition of all immune effectors that mediate graft rejection. The inhibitory functions of HLA-G were studied in vitro using allo- and xeno-geneic models, ex vivo on transplanted tissues biopsies, and in an in vivo animal model. In this review, we will summarize recent results which show that HLA-G acts as a regulator of immune function, seems to be directly involved in transplant acceptation, and should be taken into consideration when monitoring transplanted patients’ status. [Copyright &y& Elsevier]

We identified five novel human leukocyte antigen-G alleles with protein-modifying mutations in Caucasian and/or African populations. [ABSTRACT FROM AUTHOR]

Here we report two new non-classical class I HLA-G alleles found in the Brazilian population. [ABSTRACT FROM AUTHOR]