FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1973870087> ?p ?o ?g. }

• W1973870087 endingPage "538" @default.
• W1973870087 startingPage "534" @default.
• W1973870087 abstract "Certain genetic variants of the major histocompatibility complex (MHC) proteins are linked to increased susceptibility to autoimmune diseases. Hovhannisyan et al. propose a mechanism that accounts in part for one such association, the onset of coeliac disease, which is tightly associated with the expression of human HLA-DQ8 alleles and the mouse equivalent, IAg7 . This new work shows that the structural properties associated with the lack of an Asp57 found in all other MHC alleles alters the specificity of HLA-DQ8 and IAg7 . This leads to transaminase-mediated deamination of glutamine residues in dietary gluten peptides, causing them to bind more tightly to disease-associated MHC alleles and to mount an amplified anti-gluten response. HLA-DQ8 and IAg7 are also closely linked to type I diabetes, though it is not clear whether a similar mechanism is involved. The association of particular major histocompatibility complex (MHC) polymorphisms with susceptibility to a number of autoimmune disease has been a puzzling phenomenon. This paper proposes a mechanism that might account in part for the onset of coeliac disease. Transaminase-mediated deamination of glutamine residues in gluten peptides may cause them to bind more tightly to disease-associated MHC alleles, activating heteroclitic gluten-peptide specific T-cell autoreactivity in the gut. Major histocompatibility complex (MHC) class II alleles HLA-DQ8 and the mouse homologue I-Ag7 lacking a canonical aspartic acid residue at position β57 are associated with coeliac disease1,2 and type I diabetes3,4. However, the role of this single polymorphism in disease initiation and progression remains poorly understood. The lack of Asp 57 creates a positively charged P9 pocket, which confers a preference for negatively charged peptides. Gluten lacks such peptides, but tissue transglutaminase (TG2) introduces negatively charged residues at defined positions into gluten T-cell epitopes by deamidating specific glutamine residues5,6 on the basis of their spacing to proline residues7. The commonly accepted model, proposing that HLA-DQ8 simply favours binding of negatively charged peptides, does not take into account the fact that TG2 requires inflammation for activation8 and that T-cell responses against native gluten peptides are found9,10, particularly in children11. Here we show that β57 polymorphism promotes the recruitment of T-cell receptors bearing a negative signature charge in the complementary determining region 3β (CDR3β) during the response against native gluten peptides presented by HLA-DQ8 in coeliac disease. These T cells showed a crossreactive and heteroclitic (stronger) response to deamidated gluten peptides. Furthermore, gluten peptide deamidation extended the T-cell-receptor repertoire by relieving the requirement for a charged residue in CDR3β. Thus, the lack of a negative charge at position β57 in MHC class II was met by negatively charged residues in the T-cell receptor or in the peptide, the combination of which might explain the role of HLA-DQ8 in amplifying the T-cell response against dietary gluten." @default.
• W1973870087 created "2016-06-24" @default.
• W1973870087 creator A5002605322 @default.
• W1973870087 creator A5007598672 @default.
• W1973870087 creator A5022421180 @default.
• W1973870087 creator A5023751714 @default.
• W1973870087 creator A5029220488 @default.
• W1973870087 creator A5033610986 @default.
• W1973870087 creator A5041731742 @default.
• W1973870087 creator A5050982279 @default.
• W1973870087 creator A5060376799 @default.
• W1973870087 creator A5063320451 @default.
• W1973870087 creator A5064488610 @default.
• W1973870087 creator A5064835819 @default.
• W1973870087 creator A5081876747 @default.
• W1973870087 creator A5082292962 @default.
• W1973870087 date "2008-11-01" @default.
• W1973870087 modified "2023-10-17" @default.
• W1973870087 title "The role of HLA-DQ8 β57 polymorphism in the anti-gluten T-cell response in coeliac disease" @default.
• W1973870087 cites W1913127820 @default.
• W1973870087 cites W1973485458 @default.
• W1973870087 cites W1993159681 @default.
• W1973870087 cites W1997513762 @default.
• W1973870087 cites W2035628827 @default.
• W1973870087 cites W2036052530 @default.
• W1973870087 cites W2036253935 @default.
• W1973870087 cites W2048796508 @default.
• W1973870087 cites W2053396500 @default.
• W1973870087 cites W2055320452 @default.
• W1973870087 cites W2057354555 @default.
• W1973870087 cites W2063044744 @default.
• W1973870087 cites W2066626286 @default.
• W1973870087 cites W2074050058 @default.
• W1973870087 cites W2080636087 @default.
• W1973870087 cites W2080891856 @default.
• W1973870087 cites W2081913102 @default.
• W1973870087 cites W2087297634 @default.
• W1973870087 cites W2093902228 @default.
• W1973870087 cites W2106836957 @default.
• W1973870087 cites W2111078616 @default.
• W1973870087 cites W2119520032 @default.
• W1973870087 cites W2130207165 @default.
• W1973870087 cites W2132986686 @default.
• W1973870087 cites W2135292334 @default.
• W1973870087 cites W2141820146 @default.
• W1973870087 cites W2142414226 @default.
• W1973870087 cites W2162143225 @default.
• W1973870087 cites W4313333826 @default.
• W1973870087 doi "https://doi.org/10.1038/nature07524" @default.
• W1973870087 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3784325" @default.
• W1973870087 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19037317" @default.
• W1973870087 hasPublicationYear "2008" @default.
• W1973870087 type Work @default.
• W1973870087 sameAs 1973870087 @default.
• W1973870087 citedByCount "85" @default.
• W1973870087 countsByYear W19738700872012 @default.
• W1973870087 countsByYear W19738700872013 @default.
• W1973870087 countsByYear W19738700872014 @default.
• W1973870087 countsByYear W19738700872015 @default.
• W1973870087 countsByYear W19738700872016 @default.
• W1973870087 countsByYear W19738700872017 @default.
• W1973870087 countsByYear W19738700872018 @default.
• W1973870087 countsByYear W19738700872019 @default.
• W1973870087 countsByYear W19738700872020 @default.
• W1973870087 countsByYear W19738700872021 @default.
• W1973870087 countsByYear W19738700872022 @default.
• W1973870087 countsByYear W19738700872023 @default.
• W1973870087 crossrefType "journal-article" @default.
• W1973870087 hasAuthorship W1973870087A5002605322 @default.
• W1973870087 hasAuthorship W1973870087A5007598672 @default.
• W1973870087 hasAuthorship W1973870087A5022421180 @default.
• W1973870087 hasAuthorship W1973870087A5023751714 @default.
• W1973870087 hasAuthorship W1973870087A5029220488 @default.
• W1973870087 hasAuthorship W1973870087A5033610986 @default.
• W1973870087 hasAuthorship W1973870087A5041731742 @default.
• W1973870087 hasAuthorship W1973870087A5050982279 @default.
• W1973870087 hasAuthorship W1973870087A5060376799 @default.
• W1973870087 hasAuthorship W1973870087A5063320451 @default.
• W1973870087 hasAuthorship W1973870087A5064488610 @default.
• W1973870087 hasAuthorship W1973870087A5064835819 @default.
• W1973870087 hasAuthorship W1973870087A5081876747 @default.
• W1973870087 hasAuthorship W1973870087A5082292962 @default.
• W1973870087 hasBestOaLocation W19738700872 @default.
• W1973870087 hasConcept C104317684 @default.
• W1973870087 hasConcept C142724271 @default.
• W1973870087 hasConcept C147483822 @default.
• W1973870087 hasConcept C170627219 @default.
• W1973870087 hasConcept C180754005 @default.
• W1973870087 hasConcept C188280979 @default.
• W1973870087 hasConcept C203014093 @default.
• W1973870087 hasConcept C207936829 @default.
• W1973870087 hasConcept C2779134260 @default.
• W1973870087 hasConcept C2780349322 @default.
• W1973870087 hasConcept C54355233 @default.
• W1973870087 hasConcept C71924100 @default.
• W1973870087 hasConcept C86803240 @default.
• W1973870087 hasConcept C8891405 @default.
• W1973870087 hasConceptScore W1973870087C104317684 @default.

• next