PMID- 30078552
OWN - NLM
STAT- MEDLINE
DCOM- 20191022
LR  - 20201231
IS  - 1932-7420 (Electronic)
IS  - 1550-4131 (Linking)
VI  - 28
IP  - 6
DP  - 2018 Dec 4
TI  - Conventional and Neo-antigenic Peptides Presented by beta Cells Are Targeted by 
      Circulating Naive CD8+ T Cells in Type 1 Diabetic and Healthy Donors.
PG  - 946-960.e6
LID - S1550-4131(18)30450-9 [pii]
LID - 10.1016/j.cmet.2018.07.007 [doi]
AB  - Although CD8(+) T-cell-mediated autoimmune beta cell destruction occurs in type 1 
      diabetes (T1D), the target epitopes processed and presented by beta 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 beta 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 beta cells and for the development of T cell 
      biomarkers and tolerogenic vaccination strategies.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Gonzalez-Duque, Sergio
AU  - Gonzalez-Duque S
AD  - INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin 
      Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cite, 
      75014 Paris, France; ESPCI Paris, PSL University, Spectrometrie de Masse 
      Biologique et Proteomique, CNRS USR3149, 75005 Paris, France.
FAU - Azoury, Marie Eliane
AU  - Azoury ME
AD  - INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin 
      Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cite, 
      75014 Paris, France.
FAU - Colli, Maikel L
AU  - Colli ML
AD  - Universite Libre de Bruxelles Center for Diabetes Research and Welbio, Medical 
      Faculty, Universite Libre de Bruxelles, 1070 Brussels, Belgium.
FAU - Afonso, Georgia
AU  - Afonso G
AD  - INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin 
      Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cite, 
      75014 Paris, France.
FAU - Turatsinze, Jean-Valery
AU  - Turatsinze JV
AD  - Universite Libre de Bruxelles Center for Diabetes Research and Welbio, Medical 
      Faculty, Universite Libre de Bruxelles, 1070 Brussels, Belgium.
FAU - Nigi, Laura
AU  - Nigi L
AD  - University of Siena, Department of Medicine, Surgery and Neuroscience, Diabetes 
      Unit and Fondazione Umberto di Mario ONLUS, Toscana Life Sciences, 53100 Siena, 
      Italy.
FAU - Lalanne, Ana Ines
AU  - Lalanne AI
AD  - INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin 
      Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cite, 
      75014 Paris, France.
FAU - Sebastiani, Guido
AU  - Sebastiani G
AD  - University of Siena, Department of Medicine, Surgery and Neuroscience, Diabetes 
      Unit and Fondazione Umberto di Mario ONLUS, Toscana Life Sciences, 53100 Siena, 
      Italy.
FAU - Carre, Alexia
AU  - Carre A
AD  - INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin 
      Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cite, 
      75014 Paris, France.
FAU - Pinto, Sheena
AU  - Pinto S
AD  - DKFZ, Division of Developmental Immunology, 69120 Heidelberg, Germany.
FAU - Culina, Slobodan
AU  - Culina S
AD  - INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin 
      Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cite, 
      75014 Paris, France.
FAU - Corcos, Noemie
AU  - Corcos N
AD  - INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin 
      Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cite, 
      75014 Paris, France.
FAU - Bugliani, Marco
AU  - Bugliani M
AD  - University of Pisa, Department of Clinical and Experimental Medicine, 56124 Pisa, 
      Italy.
FAU - Marchetti, Piero
AU  - Marchetti P
AD  - University of Pisa, Department of Clinical and Experimental Medicine, 56124 Pisa, 
      Italy.
FAU - Armanet, Mathieu
AU  - Armanet M
AD  - Assistance Publique Hopitaux de Paris, Cell Therapy Unit, Saint Louis Hospital, 
      75010 Paris, France.
FAU - Diedisheim, Marc
AU  - Diedisheim M
AD  - INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin 
      Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cite, 
      75014 Paris, France; Assistance Publique Hopitaux de Paris, Service de 
      Diabetologie, Cochin Hospital, 75014 Paris, France.
FAU - Kyewski, Bruno
AU  - Kyewski B
AD  - DKFZ, Division of Developmental Immunology, 69120 Heidelberg, Germany.
FAU - Steinmetz, Lars M
AU  - Steinmetz LM
AD  - 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.
FAU - Buus, Soren
AU  - Buus S
AD  - Panum Institute, Department of International Health, Immunology and Microbiology, 
      2200 Copenhagen, Denmark.
FAU - You, Sylvaine
AU  - You S
AD  - INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin 
      Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cite, 
      75014 Paris, France.
FAU - Dubois-Laforgue, Daniele
AU  - Dubois-Laforgue D
AD  - INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin 
      Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cite, 
      75014 Paris, France; Assistance Publique Hopitaux de Paris, Service de 
      Diabetologie, Cochin Hospital, 75014 Paris, France.
FAU - Larger, Etienne
AU  - Larger E
AD  - INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin 
      Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cite, 
      75014 Paris, France; Assistance Publique Hopitaux de Paris, Service de 
      Diabetologie, Cochin Hospital, 75014 Paris, France.
FAU - Beressi, Jean-Paul
AU  - Beressi JP
AD  - Centre Hospitalier de Versailles Andre Mignot, Service de Diabetologie, 78150 Le 
      Chesnay, France.
FAU - Bruno, Graziella
AU  - Bruno G
AD  - University of Turin, Department of Medical Sciences, 10126 Turin, Italy.
FAU - Dotta, Francesco
AU  - Dotta F
AD  - University of Siena, Department of Medicine, Surgery and Neuroscience, Diabetes 
      Unit and Fondazione Umberto di Mario ONLUS, Toscana Life Sciences, 53100 Siena, 
      Italy.
FAU - Scharfmann, Raphael
AU  - Scharfmann R
AD  - INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin 
      Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cite, 
      75014 Paris, France.
FAU - Eizirik, Decio L
AU  - Eizirik DL
AD  - Universite Libre de Bruxelles Center for Diabetes Research and Welbio, Medical 
      Faculty, Universite Libre de Bruxelles, 1070 Brussels, Belgium.
FAU - Verdier, Yann
AU  - Verdier Y
AD  - ESPCI Paris, PSL University, Spectrometrie de Masse Biologique et Proteomique, 
      CNRS USR3149, 75005 Paris, France.
FAU - Vinh, Joelle
AU  - Vinh J
AD  - ESPCI Paris, PSL University, Spectrometrie de Masse Biologique et Proteomique, 
      CNRS USR3149, 75005 Paris, France.
FAU - Mallone, Roberto
AU  - Mallone R
AD  - INSERM, U1016, Cochin Institute, 75014 Paris, France; CNRS, UMR8104, Cochin 
      Institute, 75014 Paris, France; Paris Descartes University, Sorbonne Paris Cite, 
      75014 Paris, France; Assistance Publique Hopitaux de Paris, Service de 
      Diabetologie, Cochin Hospital, 75014 Paris, France. Electronic address: 
      roberto.mallone@inserm.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180802
PL  - United States
TA  - Cell Metab
JT  - Cell metabolism
JID - 101233170
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA Antigens)
RN  - 0 (Insulin)
RN  - 0 (Islet Amyloid Polypeptide)
RN  - 0 (Neuroendocrine Secretory Protein 7B2)
RN  - 0 (Protein Precursors)
RN  - 0 (SCG5 protein, human)
RN  - 0 (UCN3 protein, human)
RN  - 0 (Urocortins)
RN  - 61116-24-3 (preproinsulin)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
RN  - EC 3.4.21.94 (PCSK2 protein, human)
RN  - EC 3.4.21.94 (Proprotein Convertase 2)
SB  - IM
MH  - Animals
MH  - *Antigen Presentation
MH  - Biomarkers/metabolism
MH  - CD8-Positive T-Lymphocytes/cytology/*immunology/metabolism
MH  - Case-Control Studies
MH  - Cell Line
MH  - Corticotropin-Releasing Hormone/metabolism
MH  - Cytokines/metabolism
MH  - Diabetes Mellitus, Type 1/*immunology
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - HLA Antigens/metabolism
MH  - Humans
MH  - Insulin/metabolism
MH  - Islet Amyloid Polypeptide/metabolism
MH  - Mice
MH  - Neuroendocrine Secretory Protein 7B2/metabolism
MH  - Proprotein Convertase 2/metabolism
MH  - Protein Precursors/metabolism
MH  - Proteomics/methods
MH  - Transcriptome/*immunology
MH  - Urocortins/metabolism
OTO - NOTNLM
OT  - antigen
OT  - autoimmunity
OT  - epitope
OT  - human leukocyte antigen (HLA)
OT  - preproinsulin
OT  - proconvertase
OT  - secretogranin
OT  - transpeptidation
OT  - type 1 diabetes
OT  - urocortin
EDAT- 2018/08/07 06:00
MHDA- 2019/10/23 06:00
CRDT- 2018/08/07 06:00
PHST- 2018/01/02 00:00 [received]
PHST- 2018/05/20 00:00 [revised]
PHST- 2018/07/11 00:00 [accepted]
PHST- 2018/08/07 06:00 [pubmed]
PHST- 2019/10/23 06:00 [medline]
PHST- 2018/08/07 06:00 [entrez]
AID - S1550-4131(18)30450-9 [pii]
AID - 10.1016/j.cmet.2018.07.007 [doi]
PST - ppublish
SO  - Cell Metab. 2018 Dec 4;28(6):946-960.e6. doi: 10.1016/j.cmet.2018.07.007. Epub 
      2018 Aug 2.