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The role of HLA-DQ8 β57 polymorphism in the anti-gluten T-cell response in coeliac disease

Author

Listed:
  • Zaruhi Hovhannisyan

    (Pathology, Pediatrics and Committee of Immunology, University of Chicago, Chicago, Illinois 60637, USA)

  • Angela Weiss

    (Princeton University, Princeton, New Jersey 08544, USA)

  • Alexandra Martin

    (Pathology, Pediatrics and Committee of Immunology, University of Chicago, Chicago, Illinois 60637, USA)

  • Martina Wiesner

    (Leiden University, 2300 RC, Leiden, The Netherlands)

  • Stig Tollefsen

    (Centre for Immune Regulation, Institute of Immunology, Rikshospitalet University Hospital)

  • Kenji Yoshida

    (The Scripps Research Institute, La Jolla, California 92037, USA)

  • Cezary Ciszewski

    (Pathology, Pediatrics and Committee of Immunology, University of Chicago, Chicago, Illinois 60637, USA)

  • Shane A. Curran

    (Pathology, Pediatrics and Committee of Immunology, University of Chicago, Chicago, Illinois 60637, USA)

  • Joseph A. Murray

    (Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA)

  • Chella S. David

    (Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA)

  • Ludvig M. Sollid

    (Centre for Immune Regulation, Institute of Immunology, Rikshospitalet University Hospital
    Centre for Immune Regulation, Institute of Immunology, University of Oslo)

  • Frits Koning

    (Leiden University, 2300 RC, Leiden, The Netherlands)

  • Luc Teyton

    (The Scripps Research Institute, La Jolla, California 92037, USA)

  • Bana Jabri

    (Pathology, Pediatrics and Committee of Immunology, University of Chicago, Chicago, Illinois 60637, USA)

Abstract

Coeliac disease onset 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.

Suggested Citation

  • Zaruhi Hovhannisyan & Angela Weiss & Alexandra Martin & Martina Wiesner & Stig Tollefsen & Kenji Yoshida & Cezary Ciszewski & Shane A. Curran & Joseph A. Murray & Chella S. David & Ludvig M. Sollid & , 2008. "The role of HLA-DQ8 β57 polymorphism in the anti-gluten T-cell response in coeliac disease," Nature, Nature, vol. 456(7221), pages 534-538, November.
    • Handle: RePEc:nat:nature:v:456:y:2008:i:7221:d:10.1038_nature07524
    DOI: 10.1038/nature07524
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