Journal Article

DKFZ-2018-02268

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Conventional and Neo-antigenic Peptides Presented by β Cells Are Targeted by Circulating Naïve CD8+ T Cells in Type 1 Diabetic and Healthy Donors.

Gonzalez-Duque, S. ; Azoury, M. E. ; Colli, M. L. ; Afonso, G. ; Turatsinze, J.-V. ; Nigi, L. ; Lalanne, A. I. ; Sebastiani, G. ; Carré, A. ; Pinto, S.DKFZ* ; Culina, S. ; Corcos, N. ; Bugliani, M. ; Marchetti, P. ; Armanet, M. ; Diedisheim, M. ; Kyewski, B.DKFZ* ; Steinmetz, L. M. ; Buus, S. ; You, S. ; Dubois-Laforgue, D. ; Larger, E. ; Beressi, J.-P. ; Bruno, G. ; Dotta, F. ; Scharfmann, R. ; Eizirik, D. L. ; Verdier, Y. ; Vinh, J. ; Mallone, R.

2018
Cell Press Cambridge, Mass.

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Please use a persistent id in citations: doi:10.1016/j.cmet.2018.07.007

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.

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Contributing Institute(s):

1. Entwicklungsimmunologie (D090)

Research Program(s):

1. 314 - Tumor immunology (POF3-314) (POF3-314)

Appears in the scientific report 2018

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; IF >= 20 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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