title: Ingestion of oats and barley in patients with celiac disease mobilizes cross-reactive T cells activated by avenin peptides and immuno-dominant hordein peptides.
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.
authors.affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address: mhardy@wehi.edu.au.
authors.forename: Melinda Y
authors.initials: MY
authors.lastname: Hardy
authors.affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia; Department of Gastroenterology, The Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050, Australia. Electronic address: tyedin@wehi.edu.au.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Tye-Din
authors.affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia. Electronic address: Jessica.stewart@ppdi.com.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Stewart
authors.affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia. Electronic address: F.schmitz@lumc.nl.
authors.forename: Frederike
authors.initials: F
authors.lastname: Schmitz
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia. Electronic address: Nadine.Dudek@monash.edu.
authors.forename: Nadine L
authors.initials: NL
authors.lastname: Dudek
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia. Electronic address: iresha.hanchapola@monash.edu.
authors.forename: Iresha
authors.initials: I
authors.lastname: Hanchapola
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia. Electronic address: Anthony.purcell@monash.edu.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Purcell
authors.affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia; ImmusanT, Inc., One Kendall Square, Building 200, LL, Suite 4, Cambridge, MA 02139, USA. Electronic address: bob@immusant.com.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Anderson
mesh_terms: D000595:Amino Acid Sequence; D018554:Avena / Q000737:chemistry; D002446:Celiac Disease / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology*; D004435:Eating; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D005983:Glutens / Q000737:chemistry; D001467:Hordeum / Q000737:chemistry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D055315:Prolamins / Q000737:chemistry; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D055315:Prolamins; D005983:Glutens
keywords: Avenin; Celiac disease; Oats; T cells