title: Consistency in polyclonal T-cell responses to gluten between children and adults with celiac disease.
abstract: OBJECTIVE
  Developing antigen-specific approaches for diagnosis and treatment of celiac disease requires a detailed understanding of the specificity of T cells for gluten. The existing paradigm is that T-cell lines and clones from children differ from those of adults in the hierarchy and diversity of peptide recognition. We aimed to characterize the T-cell response to gluten in children vs adults with celiac disease.
  
  
  METHODS
  Forty-one children with biopsy-proven celiac disease (median age, 9 years old; 17 male), who had been on strict gluten-free diets for at least 3 months, were given a 3-day challenge with wheat; blood samples were collected and gluten-specific T cells were measured. We analyzed responses of T cells from these children and from 4 adults with celiac disease to a peptide library and measured T-cell receptor bias. We isolated T-cell clones that recognized dominant peptides and assessed whether gluten peptide recognition was similar between T-cell clones from children and adults.
  
  
  RESULTS
  We detected gluten-specific responses by T cells from 30 of the children with celiac disease (73%). T cells from the children recognized the same peptides that were immunogenic to adults with celiac disease; deamidation of peptides increased these responses. Age and time since diagnosis did not affect the magnitude of T-cell responses to dominant peptides. T-cell clones specific for dominant α- or ω-gliadin peptides from children with celiac disease had comparable levels of reactivity to wheat, rye, and barley peptides as T-cell clones from adults with celiac disease. The α-gliadin-specific T cells from children had biases in T-cell receptor usage similar to those in adults.
  
  
  CONCLUSIONS
  T cells from children with celiac disease recognize similar gluten peptides as T cells from adults with celiac disease. The findings indicate that peptide-based diagnostics and therapeutics for adults may also be used for children.
authors.affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Melinda Y
authors.initials: MY
authors.lastname: Hardy
authors.affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Adam
authors.initials: A
authors.lastname: Girardin
authors.affiliation: Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Gastroenterology, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
authors.forename: Catherine
authors.initials: C
authors.lastname: Pizzey
authors.affiliation: Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Melbourne, Victoria, Australia.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Cameron
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Watson
authors.affiliation: Institute of Protein Biochemistry-CNR, Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Picascia
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: Auricchio
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Greco
authors.affiliation: Institute of Protein Biochemistry-CNR, Naples, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Gianfrani
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: La Gruta
authors.affiliation: ImmusanT, Inc., Cambridge, Massachusetts.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Anderson
authors.affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia; Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Gastroenterology, The Royal Melbourne Hospital, Parkville, Victoria, Australia. Electronic address: tyedin@wehi.edu.au.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Tye-Din
mesh_terms: D000328:Adult; D000367:Age Factors; D000375:Aging / Q000276:immunology*; D002446:Celiac Disease / Q000175:diagnosis* / Q000276:immunology*; D002648:Child; D002999:Clone Cells / Q000276:immunology; D055050:Diet, Gluten-Free; D005260:Female; D005983:Glutens / Q000276:immunology*; D006801:Humans; D008297:Male; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
chemical_list: D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D005983:Glutens
keywords: Food Intolerance Mechanisms; Immune Response; Immunity; Pediatric; T-Cell Epitope