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Pathogenic CD4 T cells in type 1 diabetes recognize epitopes formed by peptide fusion.
Delong, Thomas; Wiles, Timothy A; Baker, Rocky L; Bradley, Brenda; Barbour, Gene; Reisdorph, Richard; Armstrong, Michael; Powell, Roger L; Reisdorph, Nichole; Kumar, Nitesh; Elso, Colleen M; DeNicola, Megan; Bottino, Rita; Powers, Alvin C; Harlan, David M; Kent, Sally C; Mannering, Stuart I; Haskins, Kathryn.
Afiliación
  • Delong T; Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, Anschutz Medical Campus, Aurora, CO 80045, USA. thomas.delong@ucdenver.edu katie.haskins@ucdenver.edu.
  • Wiles TA; Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Baker RL; Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Bradley B; Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Barbour G; Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Reisdorph R; Pharmaceutical Sciences, University of Colorado School of Medicine, Aurora, CO 80045, USA.
  • Armstrong M; Pharmaceutical Sciences, University of Colorado School of Medicine, Aurora, CO 80045, USA.
  • Powell RL; Pharmaceutical Sciences, University of Colorado School of Medicine, Aurora, CO 80045, USA.
  • Reisdorph N; Pharmaceutical Sciences, University of Colorado School of Medicine, Aurora, CO 80045, USA.
  • Kumar N; Immunology and Diabetes Unit, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia.
  • Elso CM; Immunology and Diabetes Unit, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia.
  • DeNicola M; Department of Medicine, Diabetes Division, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USA.
  • Bottino R; Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Allegheny Health Network, Pittsburgh, PA, USA.
  • Powers AC; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, and Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA. VA Tennessee Valley Healthcare System, Nashville, TN, USA.
  • Harlan DM; Department of Medicine, Diabetes Division, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USA.
  • Kent SC; Department of Medicine, Diabetes Division, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USA.
  • Mannering SI; Immunology and Diabetes Unit, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia. University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria 3065, Australia.
  • Haskins K; Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, Anschutz Medical Campus, Aurora, CO 80045, USA. thomas.delong@ucdenver.edu katie.haskins@ucdenver.edu.
Science ; 351(6274): 711-4, 2016 Feb 12.
Article en En | MEDLINE | ID: mdl-26912858
T cell-mediated destruction of insulin-producing ß cells in the pancreas causes type 1 diabetes (T1D). CD4 T cell responses play a central role in ß cell destruction, but the identity of the epitopes recognized by pathogenic CD4 T cells remains unknown. We found that diabetes-inducing CD4 T cell clones isolated from nonobese diabetic mice recognize epitopes formed by covalent cross-linking of proinsulin peptides to other peptides present in ß cell secretory granules. These hybrid insulin peptides (HIPs) are antigenic for CD4 T cells and can be detected by mass spectrometry in ß cells. CD4 T cells from the residual pancreatic islets of two organ donors who had T1D also recognize HIPs. Autoreactive T cells targeting hybrid peptides may explain how immune tolerance is broken in T1D.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptido C / Linfocitos T CD4-Positivos / Diabetes Mellitus Experimental / Diabetes Mellitus Tipo 1 / Células Secretoras de Insulina / Epítopos Límite: Animals Idioma: En Revista: Science Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptido C / Linfocitos T CD4-Positivos / Diabetes Mellitus Experimental / Diabetes Mellitus Tipo 1 / Células Secretoras de Insulina / Epítopos Límite: Animals Idioma: En Revista: Science Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos