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Proc Natl Acad Sci U S A. 2019 Jul 8. pii: 201901561. doi: 10.1073/pnas.1901561116. [Epub ahead of print]

Efficient T cell-B cell collaboration guides autoantibody epitope bias and onset of celiac disease.

Author information

1
KG Jebsen Coeliac Disease Research Centre, University of Oslo, NO-0372 Oslo, Norway; rasmus.iversen@medisin.uio.no l.m.sollid@medisin.uio.no.
2
Department of Immunology, Oslo University Hospital, NO-0372 Oslo, Norway.
3
KG Jebsen Coeliac Disease Research Centre, University of Oslo, NO-0372 Oslo, Norway.
4
Celiac Disease Center, Heim Pál National Pediatric Institute, HU-1089 Budapest, Hungary.
5
Department of Gastroenterology, Oslo University Hospital, NO-0372 Oslo, Norway.

Abstract

B cells play important roles in autoimmune diseases through autoantibody production, cytokine secretion, or antigen presentation to T cells. In most cases, the contribution of B cells as antigen-presenting cells is not well understood. We have studied the autoantibody response against the enzyme transglutaminase 2 (TG2) in celiac disease patients by generating recombinant antibodies from single gut plasma cells reactive with discrete antigen domains and by undertaking proteomic analysis of anti-TG2 serum antibodies. The majority of the cells recognized epitopes in the N-terminal domain of TG2. Antibodies recognizing C-terminal epitopes interfered with TG2 cross-linking activity, and B cells specific for C-terminal epitopes were inefficient at taking up TG2-gluten complexes for presentation to gluten-specific T cells. The bias toward N-terminal epitopes hence reflects efficient T-B collaboration. Production of antibodies against N-terminal epitopes coincided with clinical onset of disease, suggesting that TG2-reactive B cells with certain epitope specificities could be the main antigen-presenting cells for pathogenic, gluten-specific T cells. The link between B cell epitopes, antigen presentation, and disease onset provides insight into the pathogenic mechanisms of a T cell-mediated autoimmune condition.

KEYWORDS:

B cells; antigen presentation; autoantibodies; celiac disease

PMID:
31285344
DOI:
10.1073/pnas.1901561116

Conflict of interest statement

The authors declare no conflict of interest.

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