Ingestion of oats and barley in patients with celiac disease mobilizes cross-reactive T cells activated by avenin peptides and immuno-dominant hordein peptides. (January 2015)

• Record Type: Journal Article
• Authors: Hardy, Melinda Y.; Tye-Din, Jason A.; Stewart, Jessica A.; Schmitz, Frederike; Dudek, Nadine L.; Hanchapola, Iresha; Purcell, Anthony W.; Anderson, Robert P.
• Is Part Of: Journal of autoimmunity. Volume 56(2015)
• Page Start: 56
• Page End: 65
• Publication Date: 2015-01
• Subjects: Oats -- Avenin -- Celiac disease -- T cells; CD celiac disease -- GFD gluten-free diet -- HLA human leukocyte antigen -- tTG tissue transglutaminase -- TCLs T cell lines -- TCCs T cell clones; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2014.10.003
• Languages: English
• ISSNs: 0896-8411

Abstract

Abstract: Celiac disease (CD) is a common CD4 + T cell mediated enteropathy driven by gluten in wheat, rye, and barley. Whilst clinical feeding studies generally support the safety of oats ingestion in CD, the avenin protein from oats can stimulate intestinal gluten-reactive T cells isolated from some CD patients in vitro . Our objective was to establish whether ingestion of oats or other grains toxic in CD stimulate an avenin-specific T cell response in vivo . We fed participants a meal of oats (100 g/day over 3 days) to measure the in vivo polyclonal avenin-specific T cell responses to peptides contained within comprehensive avenin peptide libraries in 73 HLA-DQ2.5 + CD patients. Grain cross-reactivity was investigated using oral challenge with wheat, barley, and rye. Avenin-specific responses were observed in 6/73 HLA-DQ2.5 + CD patients (8%), against four closely related peptides. Oral barley challenge efficiently induced cross-reactive avenin/hordein-specific T cells in most CD patients, whereas wheat or rye challenge did not. In vitro, immunogenic avenin peptides were susceptible to digestive endopeptidases and showed weak HLA-DQ2.5 binding stability. Our findings indicate that CD patients possess T cells capable of responding to immuno-dominant hordein epitopes and homologous avenin peptides ex vivo, but the frequency and consistency of these T cells in blood is substantially higher after oral challenge with barley compared to oats. The low rates of T cell activation after a substantial oats challenge (100 g/d) suggests that doses of oats commonly consumed are insufficient to cause clinical relapse, and supports the safety of oats demonstrated in long-term feeding studies. Highlights: Oats ingestion mobilizes avenin-specific T cells in 8% of CD patients in vivo . Barley, but not wheat or rye, mobilizes T cells that cross-react with avenin. Barley stimulates an avenin-specific T cell response in most CD patients. Protease sensitivity and lower HLA binding reduce the immunoreactivity of avenin. Low-level oats consumption may be insufficient for clinical relapse in CD patients.