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000142038 0247_ $$2doi$$a10.1016/j.cmet.2018.07.007
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000142038 037__ $$aDKFZ-2018-02268
000142038 041__ $$aeng
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000142038 1001_ $$aGonzalez-Duque, Sergio$$b0
000142038 245__ $$aConventional and Neo-antigenic Peptides Presented by β Cells Are Targeted by Circulating Naïve CD8+ T Cells in Type 1 Diabetic and Healthy Donors.
000142038 260__ $$aCambridge, Mass.$$bCell Press$$c2018
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000142038 520__ $$aAlthough CD8+ T-cell-mediated autoimmune β cell destruction occurs in type 1 diabetes (T1D), the target epitopes processed and presented by β cells are unknown. To identify them, we combined peptidomics and transcriptomics strategies. Inflammatory cytokines increased peptide presentation in vitro, paralleling upregulation of human leukocyte antigen (HLA) class I expression. Peptide sources featured several insulin granule proteins and all known β cell antigens, barring islet-specific glucose-6-phosphatase catalytic subunit-related protein. Preproinsulin yielded HLA-A2-restricted epitopes previously described. Secretogranin V and its mRNA splice isoform SCG5-009, proconvertase-2, urocortin-3, the insulin gene enhancer protein ISL-1, and an islet amyloid polypeptide transpeptidation product emerged as antigens processed into HLA-A2-restricted epitopes, which, as those already described, were recognized by circulating naive CD8+ T cells in T1D and healthy donors and by pancreas-infiltrating cells in T1D donors. This peptidome opens new avenues to understand antigen processing by β cells and for the development of T cell biomarkers and tolerogenic vaccination strategies.
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000142038 7001_ $$aAzoury, Marie Eliane$$b1
000142038 7001_ $$aColli, Maikel L$$b2
000142038 7001_ $$aAfonso, Georgia$$b3
000142038 7001_ $$aTuratsinze, Jean-Valery$$b4
000142038 7001_ $$aNigi, Laura$$b5
000142038 7001_ $$aLalanne, Ana Ines$$b6
000142038 7001_ $$aSebastiani, Guido$$b7
000142038 7001_ $$aCarré, Alexia$$b8
000142038 7001_ $$0P:(DE-He78)d2f9dbffa7b9a979f9bc4d81e769497e$$aPinto, Sheena$$b9$$udkfz
000142038 7001_ $$aCulina, Slobodan$$b10
000142038 7001_ $$aCorcos, Noémie$$b11
000142038 7001_ $$aBugliani, Marco$$b12
000142038 7001_ $$aMarchetti, Piero$$b13
000142038 7001_ $$aArmanet, Mathieu$$b14
000142038 7001_ $$aDiedisheim, Marc$$b15
000142038 7001_ $$0P:(DE-He78)08a57258198dcedd8ff8ac7eef40341a$$aKyewski, Bruno$$b16$$udkfz
000142038 7001_ $$aSteinmetz, Lars M$$b17
000142038 7001_ $$aBuus, Søren$$b18
000142038 7001_ $$aYou, Sylvaine$$b19
000142038 7001_ $$aDubois-Laforgue, Daniele$$b20
000142038 7001_ $$aLarger, Etienne$$b21
000142038 7001_ $$aBeressi, Jean-Paul$$b22
000142038 7001_ $$aBruno, Graziella$$b23
000142038 7001_ $$aDotta, Francesco$$b24
000142038 7001_ $$aScharfmann, Raphael$$b25
000142038 7001_ $$aEizirik, Decio L$$b26
000142038 7001_ $$aVerdier, Yann$$b27
000142038 7001_ $$aVinh, Joelle$$b28
000142038 7001_ $$aMallone, Roberto$$b29
000142038 773__ $$0PERI:(DE-600)2174469-5$$a10.1016/j.cmet.2018.07.007$$gVol. 28, no. 6, p. 946 - 960.e6$$n6$$p946 - 960.e6$$tCell metabolism$$v28$$x1550-4131$$y2018
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