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

• Published in: Nature communications Vol. 5; no. 1; p. 4041
• Main Authors: Steinsbø, Øyvind, Dunand, Carole J. Henry, Huang, Min, Mesin, Luka, Salgado-Ferrer, Marlene, Lundin, Knut E. A., Jahnsen, Jørgen, Wilson, Patrick C., Sollid, Ludvig M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.06.2014; Nature Publishing Group; Nature Pub. Group
• Subjects: 13/1; 13/106; 13/109; 13/31; 38/77; 38/90; 38/91; 631/250/1619/40/1742; 631/250/2152/2040; 631/250/249/1313/1357; 631/250/347; Amino Acid Sequence; Antigens; Biopsy; Celiac disease; Celiac Disease - immunology; Cloning; Diet; Epitopes - chemistry; Epitopes - immunology; Gastroenterology; Gliadin - immunology; Gluten; Humanities and Social Sciences; Humans; Immunoglobulin A - immunology; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Heavy Chains - immunology; Immunoglobulin Light Chains - genetics; Immunoglobulin Light Chains - immunology; Immunology; Lymphocytes; Monoclonal antibodies; multidisciplinary; Mutation; Peptides; Plasma; Plasma Cells - immunology; Science; Science (multidisciplinary); Norway
• DOI: 10.1038/ncomms5041
• ISSN: 2041-1723

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. Coeliac disease is characterized by an inappropriate immune response to dietary gluten proteins, involving the production of antibodies reactive to gluten. Here, the authors study the intestinal antibody response against gluten and show that gluten-specific antibodies have a low degree of somatic hypermutations.