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2nna

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==Overview==
==Overview==
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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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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==
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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]]
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[[Category: Anderson, R.P.]]
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[[Category: Anderson, R P.]]
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[[Category: Henderson, K.N.]]
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[[Category: Henderson, K N.]]
[[Category: Rossjohn, J.]]
[[Category: Rossjohn, J.]]
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[[Category: Tye-Din, J.A.]]
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[[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]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:46:10 2008''
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''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


2nna, resolution 2.10Å

Drag the structure with the mouse to rotate

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

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