Peptides Derived From Insulin Granule Proteins Are Targeted by CD8 + T Cells Across MHC Class I Restrictions in Humans and NOD Mice
| العنوان: | Peptides Derived From Insulin Granule Proteins Are Targeted by CD8 + T Cells Across MHC Class I Restrictions in Humans and NOD Mice |
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| المؤلفون: | Joëlle Vinh, Aurore Pais, Sylvaine You, Etienne Larger, Decio L. Eizirik, Maikel Luis Colli, Laure Alexandre-Heymann, Danièle Dubois-Laforgue, Roberto Mallone, Søren Buus, Georgia Afonso, Graziella Bruno, Mahmoud Tarayrah, Cassandra Lavaud, Gonzalez-Duque Sergio, Jean-Paul Beressi, Sheena Pinto, Marie Eliane Azoury, Claire Maillard, Verdier Yann |
| المساهمون: | Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Université libre de Bruxelles (ULB), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Spectrométrie de Masse Biologique et Protéomique (USR3149 / FRE2032) (SMBP), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of Copenhagen = Københavns Universitet (UCPH), Centre Hospitalier de Versailles André Mignot (CHV), Università degli studi di Torino = University of Turin (UNITO), YOU, Sylvaine, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Paris (UP), University of Copenhagen = Københavns Universitet (KU), University of Turin, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Diabetes Research and Welbio [Brussels, Belgium] (Medical Faculty), INSERM U1016, Institut Cochin, Paris, France |
| المصدر: | Diabetes Diabetes, 2020, 69 (12), pp.2678-2690. ⟨10.2337/db20-0013⟩ Diabetes, American Diabetes Association, 2020, 69 (12), pp.2678-2690. ⟨10.2337/db20-0013⟩ |
| بيانات النشر: | HAL CCSD, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, biology, Effector, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, Human leukocyte antigen, Nod, Epitope, Cell biology, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, MHC class I, Internal Medicine, biology.protein, Cytotoxic T cell, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, ComputingMilieux_MISCELLANEOUS, CD8, NOD mice |
| الوصف: | The antigenic peptides processed by β cells and presented through surface HLA Class I molecules are poorly characterized. Each HLA variant, e.g. the most common HLA-A2 and HLA-A3, carries some peptide-binding specificity. Hence, features that, despite these specificities, remain shared across variants may reveal factors favoring β-cell immunogenicity. Building on our previous description of the HLA-A2/A3 peptidome of β cells, we analyzed the HLA-A3-restricted peptides targeted by circulating CD8+ T cells. Several peptides were recognized by CD8+ T cells within a narrow frequency (1-50/106), which was similar in donors with and without type 1 diabetes and harbored variable effector/memory fractions. These epitopes could be classified as conventional peptides or neo-epitopes, generated either via peptide cis-splicing or mRNA splicing, e.g. secretogranin-5 (SCG5)-009. As reported for HLA-A2-restricted peptides, several epitopes originated from β-cell granule proteins, e.g. SCG3, SCG5 and urocortin-3. Similarly, H-2Kd-restricted CD8+ T cells recognizing the murine orthologues of SCG5, urocortin-3, and proconvertase-2 infiltrated the islets of NOD mice and transferred diabetes into NOD/scid recipients. The finding of granule proteins targeted in both humans and NOD mice supports their disease relevance and identifies the insulin granule as a rich source of epitopes, possibly reflecting its impaired processing in type 1 diabetes. |
| اللغة: | English |
| تدمد: | 0012-1797 1939-327X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c1a19452588c10d10f72a2c18829d5eTest https://www.hal.inserm.fr/inserm-03312401Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1c1a19452588c10d10f72a2c18829d5e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00121797 1939327X |
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