2nna
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The risk of celiac disease is strongly associated with human leukocyte | + | The risk of celiac disease is strongly associated with human leukocyte antigen (HLA) DQ2 and to a lesser extent with HLA DQ8. Although the pathogenesis of HLA-DQ2-mediated celiac disease is established, the underlying basis for HLA-DQ8-mediated celiac disease remains unclear. We showed that T helper 1 (Th1) responses in HLA-DQ8-associated celiac pathology were indeed HLA DQ8 restricted and that multiple, mostly deamidated peptides derived from protease-sensitive sites of gliadin were recognized. This pattern of reactivity contrasted with the more absolute deamidation dependence and relative protease resistance of the dominant gliadin peptide in DQ2-mediated disease. We provided a structural basis for the selection of HLA-DQ8-restricted, deamidated gliadin peptides. The data established that the molecular mechanisms underlying HLA-DQ8-mediated celiac disease differed markedly from the HLA-DQ2-mediated form of the disease. Accordingly, nondietary therapeutic interventions in celiac disease might need to be tailored to the genotype of the individual. |
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| + | ==Disease== | ||
| + | Known diseases associated with this structure: Celiac disease, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=146880 146880]], Celiac disease, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604305 604305]], Creutzfeldt-Jakob disease, variant, resistance to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604305 604305]], Multiple sclerosis, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604305 604305]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Anderson, R | + | [[Category: Anderson, R P.]] |
| - | [[Category: Henderson, K | + | [[Category: Henderson, K N.]] |
[[Category: Rossjohn, J.]] | [[Category: Rossjohn, J.]] | ||
| - | [[Category: Tye-Din, J | + | [[Category: Tye-Din, J A.]] |
[[Category: deamidated gluten peptide]] | [[Category: deamidated gluten peptide]] | ||
[[Category: immune system]] | [[Category: immune system]] | ||
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[[Category: post translational modification]] | [[Category: post translational modification]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:08:42 2008'' |
Revision as of 16:08, 21 February 2008
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Structure of the MHC class II molecule HLA-DQ8 bound with a deamidated gluten peptide
Contents |
Overview
The risk of celiac disease is strongly associated with human leukocyte antigen (HLA) DQ2 and to a lesser extent with HLA DQ8. Although the pathogenesis of HLA-DQ2-mediated celiac disease is established, the underlying basis for HLA-DQ8-mediated celiac disease remains unclear. We showed that T helper 1 (Th1) responses in HLA-DQ8-associated celiac pathology were indeed HLA DQ8 restricted and that multiple, mostly deamidated peptides derived from protease-sensitive sites of gliadin were recognized. This pattern of reactivity contrasted with the more absolute deamidation dependence and relative protease resistance of the dominant gliadin peptide in DQ2-mediated disease. We provided a structural basis for the selection of HLA-DQ8-restricted, deamidated gliadin peptides. The data established that the molecular mechanisms underlying HLA-DQ8-mediated celiac disease differed markedly from the HLA-DQ2-mediated form of the disease. Accordingly, nondietary therapeutic interventions in celiac disease might need to be tailored to the genotype of the individual.
Disease
Known diseases associated with this structure: Celiac disease, susceptibility to OMIM:[146880], Celiac disease, susceptibility to OMIM:[604305], Creutzfeldt-Jakob disease, variant, resistance to OMIM:[604305], Multiple sclerosis, susceptibility to OMIM:[604305]
About this Structure
2NNA is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
A structural and immunological basis for the role of human leukocyte antigen DQ8 in celiac disease., Henderson KN, Tye-Din JA, Reid HH, Chen Z, Borg NA, Beissbarth T, Tatham A, Mannering SI, Purcell AW, Dudek NL, van Heel DA, McCluskey J, Rossjohn J, Anderson RP, Immunity. 2007 Jul;27(1):23-34. Epub 2007 Jul 12. PMID:17629515
Page seeded by OCA on Thu Feb 21 18:08:42 2008
