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Restricted VH/VL usage and limited mutations in gluten-specific IgA of coeliac disease lesion plasma cells

Author

Listed:
  • Øyvind Steinsbø

    (University of Oslo and Oslo University Hospital-Rikshospitalet)

  • Carole J. Henry Dunand

    (Section of Rheumatology, Committee on Immunology, The Knapp Center for Lupus and Immunology Research, University of Chicago)

  • Min Huang

    (Section of Rheumatology, Committee on Immunology, The Knapp Center for Lupus and Immunology Research, University of Chicago)

  • Luka Mesin

    (University of Oslo and Oslo University Hospital-Rikshospitalet)

  • Marlene Salgado-Ferrer

    (Section of Rheumatology, Committee on Immunology, The Knapp Center for Lupus and Immunology Research, University of Chicago)

  • Knut E. A. Lundin

    (University of Oslo and Oslo University Hospital-Rikshospitalet
    Oslo University Hospital-Rikshospitalet)

  • Jørgen Jahnsen

    (Akershus University Hospital)

  • Patrick C. Wilson

    (Section of Rheumatology, Committee on Immunology, The Knapp Center for Lupus and Immunology Research, University of Chicago)

  • Ludvig M. Sollid

    (University of Oslo and Oslo University Hospital-Rikshospitalet)

Abstract

Coeliac disease (CD), an enteropathy caused by cereal gluten ingestion, is characterized by CD4+ T cells recognizing deamidated gluten and by antibodies reactive to gluten or the self-antigen transglutaminase 2 (TG2). TG2-specific immunoglobulin A (IgA) of plasma cells (PCs) from CD lesions have limited somatic hypermutation (SHM). Here we report that gluten-specific IgA of lesion-resident PCs share this feature. Monoclonal antibodies were expression cloned from single PCs of patients either isolated from cultures with reactivity to complex deamidated gluten antigen or by sorting with gluten peptide tetramers. Typically, the antibodies bind gluten peptides related to T-cell epitopes and many have higher reactivity to deamidated peptides. There is restricted VH and VL combination and usage among the antibodies. Limited SHM suggests that a common factor governs the mutation level in PCs producing TG2- and gluten-specific IgA. The antibodies have potential use for diagnosis of CD and for detection of gluten.

Suggested Citation

  • Øyvind Steinsbø & Carole J. Henry Dunand & Min Huang & Luka Mesin & Marlene Salgado-Ferrer & Knut E. A. Lundin & Jørgen Jahnsen & Patrick C. Wilson & Ludvig M. Sollid, 2014. "Restricted VH/VL usage and limited mutations in gluten-specific IgA of coeliac disease lesion plasma cells," Nature Communications, Nature, vol. 5(1), pages 1-12, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5041
    DOI: 10.1038/ncomms5041
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