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  • Genes
  • Genomic wide association studies have confirmed the HLA (human leukocyte antigen) class II genes as the strongest risk factor for predisposition to RA.Using transgenic mice expressing RA-associated and resistant HLA genes, we have developed a collagen-induced arthritis (CIA) model that shares similarities with human disease in sex-bias, autoantibody profile and phenotype.Studies in animal models underscore the impact of the gut flora in extra-intestinal diseases. (nih.gov)
  • Genomic wide association studies have confirmed the HLA (human leukocyte antigen) class II genes as the strongest risk factor for predisposition to RA. (nih.gov)
  • Using transgenic mice expressing RA-associated and resistant HLA genes, we have developed a collagen-induced arthritis (CIA) model that shares similarities with human disease in sex-bias, autoantibody profile and phenotype. (nih.gov)
  • The variants are encoded by the HLA DQ genes and are the result of single nucleotide polymorphisms (SNP). (wikipedia.org)
  • DQ7 is linked by haplotype to a number of DQA1 (DQ alpha chain) genes, producing in cis-haplotype form, a large number of DQ αβ isoforms. (wikipedia.org)
  • Certain HLA DR and DQ genes have known involvement in autoimmune diseases. (wikipedia.org)
  • The DR3-DQ2 haplotype is notable because of the very strong linkage between genes that extends into the HLA-A, -B and -C regions of the HLA gene complex in northern and northwestern Europe. (wikipedia.org)
  • The linked haplotype is HLA A1-B8-DR3-DQ2 (AH8.1 in the most recent literature) Because of its strong linkage disequilbrium, each of the genes in the haplotype are markers for probable presence of adjacent genes. (wikipedia.org)
  • The response is also dependent on the genetic makeup of the human leukocyte antigen genes. (wikipedia.org)
  • molecules
  • Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. (rcsb.org)
  • To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. (rcsb.org)
  • HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. (rcsb.org)
  • In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. (rcsb.org)
  • Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading. (rcsb.org)
  • Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). (cancerindex.org)
  • Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. (cancerindex.org)
  • HLA-DQ8 and DRB1FNx010401 molecules predispose to develop arthritis while DRB1FNx010402 provides protection. (nih.gov)
  • Two types of HLA-DQ2 molecules exist, termed HLA-DQ2.5 and HLA-DQ2.2. (pnas.org)
  • HLA-DQ molecules bind and present peptides to antigen-specific T cells. (pnas.org)
  • To determine the mechanism underlying these observations we have now compared the gluten-specific T cell response in the context of the HLA-DQ2.5 and HLA-DQ2.2 molecules. (pnas.org)
  • While the DQ3 molecules are structurally similar in beta chain, the DQ molecules differ markedly in function, even when present with the same DQ alpha subunit. (wikipedia.org)
  • Human
  • Human leucocyte antigen (HLA) status has a significant role in immune responses and immunological tolerance and is a factor in the onset of type 2 diabetes. (bmj.com)
  • This is the highest phenotype frequency observed for any DR or DQ phenotype in the human population by a wide margin. (wikipedia.org)
  • In the human population DQ is highly variable, the β subunit more so than the alpha chain. (wikipedia.org)
  • genetic
  • There is the possibility it spread to Arabia, but through stepwise expansion of small groups was lost from the DQ genetic repertoire. (wikipedia.org)
  • endocytic
  • Binds peptides derived from antigens that access the endocytic route of antigen presenting cells ( APC ) and presents them on the cell surface for recognition by the CD4 T-cells. (rcsb.org)
  • cell surface
  • HLA-DQ (DQ) is a cell surface receptor protein found on antigen presenting cells. (wikipedia.org)
  • As a variable cell surface receptor on immune cells, these D antigens, originally HL-A4 antigens, are involved in graft versus host disease when lymphoid tissues are transplanted between people. (wikipedia.org)
  • HLA DQ functions as a cell surface receptor for foreign or self antigens. (wikipedia.org)
  • The protein encoded by this gene is one of two proteins that are required to form the DQ heterodimer, a cell surface receptor essential to the function of the immune system. (wikipedia.org)
  • Protein
  • Others result in changes in regions that are removed when the proteins is processed to the cell surface, still others result in change in the non-functional regions of the protein, and some changes result in a change of function of the DQ isoform that is produced. (wikipedia.org)
  • molecule
  • MHC class II molecule interacts with HLA_DM, and HLA_DO in B-cells, in order to release CLIP and facilitate the binding of antigenic peptides. (rcsb.org)
  • We now provide evidence that the disease-associated HLA-DQ2.5 molecule presents a large repertoire of gluten peptides, whereas the non-disease-associated HLA-DQ2.2 molecule can present only a subset of these. (pnas.org)
  • The HLA-DQ2.5 molecule preferentially binds peptides with negatively charged amino acids at anchor positions ( 1 , 2 ). (pnas.org)
  • genotype
  • Individuals homozygous for the disease-associated HLA-DQ2.5 genotype or HLA-DQ2.2/2.5 heterozygous have the highest risk for developing CD. (pnas.org)
  • isoform
  • Much of the isoform variation in DQ is within these 'functional' regions. (wikipedia.org)
  • HLA DR3-DQ2 encodes DQ2.5cis isoform of HLA-DQ, this isoform is described frequently as 'the DQ2 isoform', but in actuality there are two major DQ2 isoform. (wikipedia.org)
  • peptide
  • Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL , leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). (rcsb.org)
  • These results correlated with peptide binding to the antigen-presenting cells. (pnas.org)
  • It is now commonly accepted that HLA-DQ2.5 can bind and present gluten peptides and that these HLA-DQ-peptide complexes induce inflammatory T cell responses, causing disease. (pnas.org)
  • In fact, HLA DQ2.2 has been shown to bind and present a gluten peptide to T cells ( 7 ). (pnas.org)
  • celiac disease
  • In patients with celiac disease, inflammatory T cell responses to HLA-DQ2-bound gluten peptides are thought to cause disease. (pnas.org)
  • Whereas HLA-DQ2.5 predisposes to celiac disease, HLA-DQ2.2 does not. (pnas.org)
  • exogenous
  • As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. (rcsb.org)
  • disparity
  • A disparity between antigen density and mean fluorescence intensity values for some alleles within an eplet group was noted, with mean fluorescence intensity values of the lowest fluorescence bead being one tenth of the highest fluorescence bead, despite the fact that the amount of antigen on these beads were not significantly different. (sigmaaldrich.com)
  • HLA disparity determines disease activity through pregnancy in women with inflammatory bowel disease. (biomedsearch.com)
  • We studied the relationship between maternal-fetal HLA disparity and IBD course. (biomedsearch.com)
  • Odds ratios were calculated comparing HLA disparity in women whose IBD improved versus those whose disease worsened or remained active. (biomedsearch.com)
  • CONCLUSION: Improvement of IBD symptoms during pregnancy is associated with disparity in HLA class II antigens between mother and fetus. (biomedsearch.com)
  • stimulation
  • Consequently, there have been various attempts to find a differential role for DQ, from presentation of special antigens to preferential stimulation of suppressor cells. (ucl.ac.uk)
  • Gluten presentation by HLA-DQ2.5/2.2 heterozygous antigen-presenting cells induced intermediate T cell stimulation. (pnas.org)
  • disease
  • Here, Daniel Altmann and colleagues critically assess these proposals and put forward the alternative hypothesis that the effect of DQ on disease susceptibility may result from a special role in shaping the T-cell receptor repertoire. (ucl.ac.uk)
  • Our findings explain the strongly increased risk of disease development for HLA-DQ2.5 homozygous and HLA-DQ2.2/2.5 heterozygous individuals, and they are indicative of a quantitative model for disease development, where HLA-DQ expression and the available number of T cell-stimulatory gluten peptides are critical limiting factors. (pnas.org)
  • A study on the relationship between HLA-DR, DQ antigen, and intracranial aneurysm in the Han nationality show DQ5 more likely, AIDP type of Guillain Barré syndrome, and irritable bowel disease but not crohn's disease in the same (Jewish) population. (wikipedia.org)
  • pathway
  • IRP targets monocytes and increases the production of IL-15 by an HLA-DQ independent pathway, a subsequent study showed that both this region and the "33mer" could create the same response, in cells from both treated coeliacs and non-coeliacs. (wikipedia.org)
  • Type
  • 7, 8 Little is known, however, about the relation between retinopathy with type 2 diabetes and the HLA antigen. (bmj.com)