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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.

SUBMITTER: Steinsbo O 

PROVIDER: S-EPMC4059925 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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

Steinsbø Øyvind Ø   Henry Dunand Carole J CJ   Huang Min M   Mesin Luka L   Salgado-Ferrer Marlene M   Lundin Knut E A KE   Jahnsen Jørgen J   Wilson Patrick C PC   Sollid Ludvig M LM  

Nature communications 20140609


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 i  ...[more]

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