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

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 156; no. 5; pp. 1428 - 1439.e10
• Main Authors: Høydahl, Lene Støkken, Richter, Lisa, Frick, Rahel, Snir, Omri, Gunnarsen, Kristin Støen, Landsverk, Ole J.B., Iversen, Rasmus, Jeliazkov, Jeliazko R., Gray, Jeffrey J., Bergseng, Elin, Foss, Stian, Qiao, Shuo-Wang, Lundin, Knut E.A., Jahnsen, Jørgen, Jahnsen, Frode L., Sandlie, Inger, Sollid, Ludvig M., Løset, Geir Åge
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2019; W. B. Saunders Company
• Subjects: Animals; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; APC; Autoimmunity; Case-Control Studies; Celiac Disease - diagnosis; Celiac Disease - diet therapy; Celiac Disease - immunology; Celiac Disease - metabolism; Cell Line; Diet, Gluten-Free; Duodenum - immunology; Duodenum - metabolism; Duodenum - pathology; Glutens - immunology; GTP-Binding Proteins - immunology; HLA-DQ Antigens - immunology; Humans; Immune Activation; Immunity, Mucosal; Immunodominant Epitopes; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Mice; Peptide Fragments - immunology; Phenotype; Plasma Cells - immunology; Plasma Cells - metabolism; TG2; Transglutaminases - immunology; Autoimmunity; TCR; LP; hIgG1; pMHC; ELISPOT; mAb; BCR; APC; MHCII; Immune Activation; Mf; TG2; DC; ELISA
• ISSN: 0016-5085; 1528-0012; 1528-0012
• DOI: 10.1053/j.gastro.2018.12.013

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. 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). 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. 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. [Display omitted]