TG2-gluten complexes as antigens for gluten-specific and transglutaminase-2 specific B cells in celiac disease

A hallmark of celiac disease is the gluten-dependent production of antibodies specific for deamidated gluten peptides (DGP) and the enzyme transglutaminase 2 (TG2). Both types of antibodies are believed to result from B cells receiving help from gluten-specific CD4+ T cells and differentiating into...

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Bibliographic Details
Published in:PloS one 2021-11, Vol.16 (11), p.e0259082-e0259082
Main Authors: Lindstad, Christian B, Dewan, Alisa E, Stamnaes, Jorunn, Sollid, Ludvig M, du Pré, M Fleur
Format: Article
Language:English
Subjects:
Animals
Antibodies
Antigens
Autoimmune diseases
B cells
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
B-Lymphocytes - pathology
Biology and Life Sciences
CD4 antigen
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - metabolism
Celiac disease
Celiac Disease - genetics
Celiac Disease - immunology
Celiac Disease - pathology
Cell differentiation
Cloning
Collaboration
Genetic aspects
Gliadin - genetics
Gliadin - immunology
Gluten
Glutens - genetics
Glutens - immunology
Health aspects
Humans
Immunoglobulins
Immunology
Lymphocytes
Lymphocytes B
Lymphocytes T
Medicine and Health Sciences
Mice
Mice, Transgenic
Peptides
Physical Sciences
Plasma cells
Protein Glutamine gamma Glutamyltransferase 2 - genetics
Protein Glutamine gamma Glutamyltransferase 2 - immunology
Proteins
Receptors, Antigen, B-Cell - genetics
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
T-Lymphocytes - pathology
Transgenic mice
Transglutaminase 2
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Summary:A hallmark of celiac disease is the gluten-dependent production of antibodies specific for deamidated gluten peptides (DGP) and the enzyme transglutaminase 2 (TG2). Both types of antibodies are believed to result from B cells receiving help from gluten-specific CD4+ T cells and differentiating into antibody-producing plasma cells. We have here studied the collaboration between DGP- and TG2-specific B cells with gluten-specific CD4+ T cells using transgenic mice expressing celiac patient-derived T-cell and B-cell receptors, as well as between B-cell transfectants and patient-derived gluten-specific T-cell clones. We show that multivalent TG2-gluten complexes are efficient antigens for both TG2-specific and DGP-specific B cells and allow both types of B cells to receive help from gluten-specific T cells of many different specificities.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0259082