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Conventional and Neo-antigenic Peptides Presented by ß Cells Are Targeted by Circulating Naïve CD8+ T Cells in Type 1 Diabetic and Healthy Donors.
Gonzalez-Duque, Sergio; Azoury, Marie Eliane; Colli, Maikel L; Afonso, Georgia; Turatsinze, Jean-Valery; Nigi, Laura; Lalanne, Ana Ines; Sebastiani, Guido; Carré, Alexia; Pinto, Sheena; Culina, Slobodan; Corcos, Noémie; Bugliani, Marco; Marchetti, Piero; Armanet, Mathieu; Diedisheim, Marc; Kyewski, Bruno; Steinmetz, Lars M; Buus, Søren; You, Sylvaine; Dubois-Laforgue, Daniele; Larger, Etienne; Beressi, Jean-Paul; Bruno, Graziella; Dotta, Francesco; Scharfmann, Raphael; Eizirik, Decio L; Verdier, Yann; Vinh, Joelle; Mallone, Roberto.
Afiliação
  • Gonzalez-Duque S; INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cité, 75014 Paris, France; ESPCI Paris, PSL University, Spectrométrie de Masse Biologique et Protéomique, CNRS USR3149, 75005 Paris, France.
  • Azoury ME; INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cité, 75014 Paris, France.
  • Colli ML; Université Libre de Bruxelles Center for Diabetes Research and Welbio, Medical Faculty, Université Libre de Bruxelles, 1070 Brussels, Belgium.
  • Afonso G; INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cité, 75014 Paris, France.
  • Turatsinze JV; Université Libre de Bruxelles Center for Diabetes Research and Welbio, Medical Faculty, Université Libre de Bruxelles, 1070 Brussels, Belgium.
  • Nigi L; University of Siena, Department of Medicine, Surgery and Neuroscience, Diabetes Unit and Fondazione Umberto di Mario ONLUS, Toscana Life Sciences, 53100 Siena, Italy.
  • Lalanne AI; INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cité, 75014 Paris, France.
  • Sebastiani G; University of Siena, Department of Medicine, Surgery and Neuroscience, Diabetes Unit and Fondazione Umberto di Mario ONLUS, Toscana Life Sciences, 53100 Siena, Italy.
  • Carré A; INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cité, 75014 Paris, France.
  • Pinto S; DKFZ, Division of Developmental Immunology, 69120 Heidelberg, Germany.
  • Culina S; INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cité, 75014 Paris, France.
  • Corcos N; INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cité, 75014 Paris, France.
  • Bugliani M; University of Pisa, Department of Clinical and Experimental Medicine, 56124 Pisa, Italy.
  • Marchetti P; University of Pisa, Department of Clinical and Experimental Medicine, 56124 Pisa, Italy.
  • Armanet M; Assistance Publique Hôpitaux de Paris, Cell Therapy Unit, Saint Louis Hospital, 75010 Paris, France.
  • Diedisheim M; INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cité, 75014 Paris, France; Assistance Publique Hôpitaux de Paris, Service de Diabétologie, Cochin Hospital, 75014 Paris, France.
  • Kyewski B; DKFZ, Division of Developmental Immunology, 69120 Heidelberg, Germany.
  • Steinmetz LM; Stanford University, School of Medicine, Department of Genetics and Stanford Genome Technology Center, Stanford, CA 94305, USA; European Molecular Biology Laboratory, Genome Biology Unit, 69117 Heidelberg, Germany.
  • Buus S; Panum Institute, Department of International Health, Immunology and Microbiology, 2200 Copenhagen, Denmark.
  • You S; INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cité, 75014 Paris, France.
  • Dubois-Laforgue D; INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cité, 75014 Paris, France; Assistance Publique Hôpitaux de Paris, Service de Diabétologie, Cochin Hospital, 75014 Paris, France.
  • Larger E; INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cité, 75014 Paris, France; Assistance Publique Hôpitaux de Paris, Service de Diabétologie, Cochin Hospital, 75014 Paris, France.
  • Beressi JP; Centre Hospitalier de Versailles André Mignot, Service de Diabétologie, 78150 Le Chesnay, France.
  • Bruno G; University of Turin, Department of Medical Sciences, 10126 Turin, Italy.
  • Dotta F; University of Siena, Department of Medicine, Surgery and Neuroscience, Diabetes Unit and Fondazione Umberto di Mario ONLUS, Toscana Life Sciences, 53100 Siena, Italy.
  • Scharfmann R; INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cité, 75014 Paris, France.
  • Eizirik DL; Université Libre de Bruxelles Center for Diabetes Research and Welbio, Medical Faculty, Université Libre de Bruxelles, 1070 Brussels, Belgium.
  • Verdier Y; ESPCI Paris, PSL University, Spectrométrie de Masse Biologique et Protéomique, CNRS USR3149, 75005 Paris, France.
  • Vinh J; ESPCI Paris, PSL University, Spectrométrie de Masse Biologique et Protéomique, CNRS USR3149, 75005 Paris, France.
  • Mallone R; INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cité, 75014 Paris, France; Assistance Publique Hôpitaux de Paris, Service de Diabétologie, Cochin Hospital, 75014 Paris, France. Electronic address:
Cell Metab ; 28(6): 946-960.e6, 2018 12 04.
Article em En | MEDLINE | ID: mdl-30078552
ABSTRACT
Although CD8+ T-cell-mediated autoimmune ß cell destruction occurs in type 1 diabetes (T1D), the target epitopes processed and presented by ß cells are unknown. To identify them, we combined peptidomics and transcriptomics strategies. Inflammatory cytokines increased peptide presentation in vitro, paralleling upregulation of human leukocyte antigen (HLA) class I expression. Peptide sources featured several insulin granule proteins and all known ß cell antigens, barring islet-specific glucose-6-phosphatase catalytic subunit-related protein. Preproinsulin yielded HLA-A2-restricted epitopes previously described. Secretogranin V and its mRNA splice isoform SCG5-009, proconvertase-2, urocortin-3, the insulin gene enhancer protein ISL-1, and an islet amyloid polypeptide transpeptidation product emerged as antigens processed into HLA-A2-restricted epitopes, which, as those already described, were recognized by circulating naive CD8+ T cells in T1D and healthy donors and by pancreas-infiltrating cells in T1D donors. This peptidome opens new avenues to understand antigen processing by ß cells and for the development of T cell biomarkers and tolerogenic vaccination strategies.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Apresentação de Antígeno / Linfócitos T CD8-Positivos / Epitopos de Linfócito T / Diabetes Mellitus Tipo 1 / Transcriptoma Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
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PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Apresentação de Antígeno / Linfócitos T CD8-Positivos / Epitopos de Linfócito T / Diabetes Mellitus Tipo 1 / Transcriptoma Idioma: En Ano de publicação: 2018 Tipo de documento: Article