Conventional and Neo-Antigenic Peptides Presented by β Cells Are Targeted by Circulating Naïve CD8+ T Cells in Type 1 Diabetic and Healthy Donors

Sergio Gonzalez-Duque 1, 2, 3 Marie Eliane Azoury 1, 2, 4 Maikel Colli 5 Georgia Afonso 1, 2, 4 Jean-Valery Turatsinze 5 Laura Nigi 6 Ana Inés Lalanne 1, 2, 4 Guido Sebastiani 6 Alexia Carré 1, 2, 4 Sheena Pinto 7 Slobodan Culina 1, 2, 4 Noémie Corcos 1, 2, 4 Marco Bugliani 8 Marc Marchetti 8 Mathieu Armanet 9 Marc Diedisheim 1, 2, 10, 4, 11 Bruno Kyewski 7 Lars Steinmetz 12, 13 Søren Buus 14 Sylvaine You 2, 1, 4 Daniele Dubois-Laforgue 2, 1, 10, 4, 11 Etienne Larger 2, 1, 10, 4, 11 Jean-Paul Beressi 15 Graziella Bruno 16 Francesco Dotta 6 Raphael Scharfmann 1, 2, 4 Decio Eizirik 5 Yann Verdier 17 Joelle Vinh 17 Roberto Mallone 1, 2, 10, 4, 11, *
Abstract : 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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [38 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01918834
Contributor : Roberto Mallone <>
Submitted on : Monday, November 12, 2018 - 12:46:10 AM
Last modification on : Monday, November 11, 2019 - 6:38:13 PM
Long-term archiving on : Wednesday, February 13, 2019 - 12:44:34 PM

Files

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

Sergio Gonzalez-Duque, Marie Eliane Azoury, Maikel Colli, Georgia Afonso, Jean-Valery Turatsinze, et al.. Conventional and Neo-Antigenic Peptides Presented by β Cells Are Targeted by Circulating Naïve CD8+ T Cells in Type 1 Diabetic and Healthy Donors. Cell Metabolism, Elsevier, 2018, 28 (6), pp.946-960. ⟨10.1016/j.cmet.2018.07.007⟩. ⟨inserm-01918834⟩

Share

Metrics

Record views

121