title: Restricted VH/VL usage and limited mutations in gluten-specific IgA of coeliac disease lesion plasma cells.
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.
authors.affiliation: Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway.
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Steinsbø
authors.affiliation: Department of Medicine, Section of Rheumatology, Committee on Immunology, The Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Carole J
authors.initials: CJ
authors.lastname: Henry Dunand
authors.affiliation: Department of Medicine, Section of Rheumatology, Committee on Immunology, The Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway.
authors.forename: Luka
authors.initials: L
authors.lastname: Mesin
authors.affiliation: Department of Medicine, Section of Rheumatology, Committee on Immunology, The Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Marlene
authors.initials: M
authors.lastname: Salgado-Ferrer
authors.affiliation: 1] Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway [2] Department of Gastroenterology, Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway.
authors.forename: Knut E A
authors.initials: KE
authors.lastname: Lundin
authors.affiliation: Division of Medicine, Department of Gastroenterology, Akershus University Hospital, 1478 Lørenskog, Norway.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Jahnsen
authors.affiliation: Department of Medicine, Section of Rheumatology, Committee on Immunology, The Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Wilson
authors.affiliation: Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway.
authors.forename: Ludvig M
authors.initials: LM
authors.lastname: Sollid
mesh_terms: D000595:Amino Acid Sequence; D002446:Celiac Disease / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005903:Gliadin / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology*; D009154:Mutation; D010950:Plasma Cells / Q000276:immunology*
chemical_list: D000939:Epitopes; D007070:Immunoglobulin A; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D005903:Gliadin