Comprehensive, Quantitative Mapping of T Cell Epitopes in Gluten in Celiac Disease

Tye-Din, JA; Stewart, JA; Dromey, JA; Beissbarth, T; van Heel, DA; Tatham, A; Henderson, K; Mannering, SI; Gianfrani, C; Jewell, DP; Hill, AVS; McCluskey, J; Rossjohn, J; Anderson, RP

Author(s): Tye-Din, JA; Stewart, JA; Dromey, JA; Beissbarth, T; van Heel, DA; Tatham, A; Henderson, K; Mannering, SI; Gianfrani, C; Jewell, DP; Hill, AVS; McCluskey, J; Rossjohn, J; Anderson, RP;
Details: Publication Year 2010-07-21,Volume 2,Issue #41,Page -
Journal Title: SCIENCE TRANSLATIONAL MEDICINE
Publication Type: Journal Article
Abstract: Celiac disease is a genetic condition that results in a debilitating immune reaction in the gut to antigens in grain. The antigenic peptides recognized by the T cells that cause this disease are incompletely defined. Our understanding of the epitopes of pathogenic CD4(+) T cells is based primarily on responses shown by intestinal T cells in vitro to hydrolysates or polypeptides of gluten, the causative antigen. A protease-resistant 33-amino acid peptide from wheat alpha-gliadin is the immunodominant antigen, but little is known about the spectrum of T cell epitopes in rye and barley or the hierarchy of immunodominance and consistency of recognition of T cell epitopes in vivo. We induced polyclonal gluten-specific T cells in the peripheral blood of celiac patients by feeding them cereal and performed a comprehensive, unbiased analysis of responses to all celiac toxic prolamins, a class of plant storage protein. The peptides that stimulated T cells were the same among patients who ate the same cereal, but were different after wheat, barley, and rye ingestion. Unexpectedly, a sequence from omega-gliadin (wheat) and C-hordein (barley) but not alpha-gliadin was immunodominant regardless of the grain consumed. Furthermore, T cells specific for just three peptides accounted for most gluten-specific T cells, and their recognition of gluten peptides was highly redundant. Our findings show that pathogenic T cells in celiac disease show limited diversity and therefore suggest that peptide-based therapeutics for this disease and potentially other strongly human leukocyte antigen-restricted immune diseases should be possible.
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Keywords: SEQUENCE-SPECIFIC PRIMERS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; ALTERED PEPTIDE LIGAND; TISSUE TRANSGLUTAMINASE; AUTOIMMUNE-DISEASES; MULTIPLE-SCLEROSIS; CEREAL TOXICITY; C-HORDEIN; PCR-SSP; IN-VIVO
Publisher's Version: https://doi.org/10.1126/scitranslmed.3001012
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2010-07-21 12:00:00