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

PLoS One. 2021 Nov 3;16(11):e0259082. doi: 10.1371/journal.pone.0259082. eCollection 2021.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Celiac Disease / genetics*
  • Celiac Disease / immunology
  • Celiac Disease / pathology
  • Gliadin / genetics
  • Gliadin / immunology
  • Glutens / genetics*
  • Glutens / immunology
  • Humans
  • Mice
  • Mice, Transgenic
  • Protein Glutamine gamma Glutamyltransferase 2 / genetics*
  • Protein Glutamine gamma Glutamyltransferase 2 / immunology
  • Receptors, Antigen, B-Cell / genetics*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology

Substances

  • Receptors, Antigen, B-Cell
  • Glutens
  • Gliadin
  • Protein Glutamine gamma Glutamyltransferase 2

Grants and funding

This work was supported by grants from the European Commission (https://ec.europa.eu/info/index_en) through project ERC-2010-Ad-268541 to L.M.S., the Research Council of Norway (https://www.forskningsradet.no/en/) through project 275053 to L.M.S., and the University of Oslo (https://www.uio.no). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.