Plasma Cells Are the Most Abundant Gluten Peptide MHC-expressing Cells in Inflamed Intestinal Tissues From Patients With Celiac Disease

Lene Støkken Høydahl, Lisa Richter, Rahel Frick, Omri Snir, Kristin Støen Gunnarsen, Ole J.B. Landsverk, Rasmus Iversen, Jeliazko R. Jeliazkov, Jeffrey J. Gray, Elin Bergseng, Stian Foss, Shuo Wang Qiao, Knut E.A. Lundin, Jørgen Jahnsen, Frode L. Jahnsen, Inger Sandlie, Ludvig M. Sollid, Geir Åge Løset

Research output: Contribution to journalArticlepeer-review

Abstract

Background & Aims: Development of celiac disease is believed to involve the transglutaminase-dependent response of CD4 + T cells toward deamidated gluten peptides in the intestinal mucosa of individuals with specific HLA-DQ haplotypes. We investigated the antigen presentation process during this mucosal immune response. Methods: We generated monoclonal antibodies (mAbs) specific for the peptide–MHC (pMHC) complex of HLA-DQ2.5 and the immunodominant gluten epitope DQ2.5-glia-α1a using phage display. We used these mAbs to assess gluten peptide presentation and phenotypes of presenting cells by flow cytometry and enzyme-linked immune absorbent spot (ELISPOT) in freshly prepared single-cell suspensions from intestinal biopsies from 40 patients with celiac disease (35 untreated and 5 on a gluten-free diet) as well as 18 subjects with confirmed noninflamed gut mucosa (controls, 12 presumed healthy, 5 undergoing pancreatoduodenectomy, and 1 with potential celiac disease). Results: Using the mAbs, we detected MHC complexes on cells from intestinal biopsies from patients with celiac disease who consume gluten, but not from patients on gluten-free diets. We found B cells and plasma cells to be the most abundant cells that present DQ2.5-glia-α1a in the inflamed mucosa. We identified a subset of plasma cells that expresses B-cell receptors (BCR) specific for gluten peptides or the autoantigen transglutaminase 2 (TG2). Expression of MHC class II (MHCII) was not restricted to these specific plasma cells in patients with celiac disease but was observed in an average 30% of gut plasma cells from patients and controls. Conclusions: A population of plasma cells from intestinal biopsies of patients with celiac disease express MHCII; this is the most abundant cell type presenting the immunodominant gluten peptide DQ2.5-glia-α1a in the tissues from these patients. These results indicate that plasma cells in the gut can function as antigen-presenting cells and might promote and maintain intestinal inflammation in patients with celiac disease or other inflammatory disorders.

Original languageEnglish (US)
Pages (from-to)1428-1439.e10
JournalGastroenterology
Volume156
Issue number5
DOIs
StatePublished - Apr 2019

Keywords

  • APC
  • Autoimmunity
  • Immune Activation
  • TG2

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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