Conventional and Neo-antigenic Peptides Presented by beta Cells Are Targeted by Circulating Naive CD8+T Cells in Type 1 Diabetic and Healthy Donors
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Conventional and Neo-antigenic Peptides Presented by beta Cells Are Targeted by Circulating Naive 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; Carre, Alexia; Pinto, Sheena; Culina, Slobodan; Corcos, Noemie; Bugliani, Marco; Marchetti, Piero; Armanet, Mathieu; Diedisheim, Marc; Kyewski, Bruno; Steinmetz, Lars M.; Buus, Soren; 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.
I: Cell Metabolism, Bind 28, Nr. 6, 2018, s. 946-960.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Conventional and Neo-antigenic Peptides Presented by beta Cells Are Targeted by Circulating Naive CD8+T Cells in Type 1 Diabetic and Healthy Donors
AU - Gonzalez-Duque, Sergio
AU - Azoury, Marie Eliane
AU - Colli, Maikel L.
AU - Afonso, Georgia
AU - Turatsinze, Jean-Valery
AU - Nigi, Laura
AU - Lalanne, Ana Ines
AU - Sebastiani, Guido
AU - Carre, Alexia
AU - Pinto, Sheena
AU - Culina, Slobodan
AU - Corcos, Noemie
AU - Bugliani, Marco
AU - Marchetti, Piero
AU - Armanet, Mathieu
AU - Diedisheim, Marc
AU - Kyewski, Bruno
AU - Steinmetz, Lars M.
AU - Buus, Soren
AU - You, Sylvaine
AU - Dubois-Laforgue, Daniele
AU - Larger, Etienne
AU - Beressi, Jean-Paul
AU - Bruno, Graziella
AU - Dotta, Francesco
AU - Scharfmann, Raphael
AU - Eizirik, Decio L.
AU - Verdier, Yann
AU - Vinh, Joelle
AU - Mallone, Roberto
PY - 2018
Y1 - 2018
N2 - Although CD8 + T-cell-mediated autoimmune β cell destruction occurs in type 1 diabetes (T1D), the target epitopes processed and presented by β 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 β 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 β cells and for the development of T cell biomarkers and tolerogenic vaccination strategies.
AB - Although CD8 + T-cell-mediated autoimmune β cell destruction occurs in type 1 diabetes (T1D), the target epitopes processed and presented by β 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 β 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 β cells and for the development of T cell biomarkers and tolerogenic vaccination strategies.
U2 - 10.1016/j.cmet.2018.07.007
DO - 10.1016/j.cmet.2018.07.007
M3 - Journal article
C2 - 30078552
VL - 28
SP - 946
EP - 960
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 6
ER -
ID: 212859916