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000167227 0247_ $$2ISSN$$a1939-327X
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000167227 037__ $$aDKFZ-2021-00212
000167227 041__ $$aeng
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000167227 1001_ $$aAzoury, Marie Eliane$$b0
000167227 245__ $$aPeptides Derived From Insulin Granule Proteins Are Targeted by CD8+ T Cells Across MHC Class I Restrictions in Humans and NOD Mice.
000167227 260__ $$aAlexandria, Va$$bAssoc.$$c2020
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000167227 500__ $$aDivision of Developmental Immunology
000167227 520__ $$aThe antigenic peptides processed by β-cells and presented through surface HLA class I molecules are poorly characterized. Each HLA variant (e.g., the most common being HLA-A2 and HLA-A3) carries some peptide-binding specificity. Hence, features that, despite these specificities, remain shared across variants may reveal factors favoring β-cell immunogenicity. Building on our previous description of the HLA-A2/A3 peptidome of β-cells, we analyzed the HLA-A3-restricted peptides targeted by circulating CD8+ T cells. Several peptides were recognized by CD8+ T cells within a narrow frequency (1-50/106), which was similar in donors with and without type 1 diabetes and harbored variable effector/memory fractions. These epitopes could be classified as conventional peptides or neoepitopes, generated either via peptide cis-splicing or mRNA splicing (e.g., secretogranin-5 [SCG5]-009). As reported for HLA-A2-restricted peptides, several epitopes originated from β-cell granule proteins (e.g., SCG3, SCG5, and urocortin-3). Similarly, H-2Kd-restricted CD8+ T cells recognizing the murine orthologs of SCG5, urocortin-3, and proconvertase-2 infiltrated the islets of NOD mice and transferred diabetes into NOD/scid recipients. The finding of granule proteins targeted in both humans and NOD mice supports their disease relevance and identifies the insulin granule as a rich source of epitopes, possibly reflecting its impaired processing in type 1 diabetes.
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000167227 650_7 $$2NLM Chemicals$$aChromogranins
000167227 650_7 $$2NLM Chemicals$$aEpitopes
000167227 650_7 $$2NLM Chemicals$$aHLA-A3 Antigen
000167227 650_7 $$2NLM Chemicals$$aInsulin
000167227 650_7 $$2NLM Chemicals$$aNeuroendocrine Secretory Protein 7B2
000167227 650_7 $$2NLM Chemicals$$aRNA, Messenger
000167227 650_7 $$2NLM Chemicals$$aUcn3 protein, mouse
000167227 650_7 $$2NLM Chemicals$$aUrocortins
000167227 650_2 $$2MeSH$$aAdult
000167227 650_2 $$2MeSH$$aAlternative Splicing
000167227 650_2 $$2MeSH$$aAnimals
000167227 650_2 $$2MeSH$$aCD8-Positive T-Lymphocytes
000167227 650_2 $$2MeSH$$aCase-Control Studies
000167227 650_2 $$2MeSH$$aChromogranins: genetics
000167227 650_2 $$2MeSH$$aChromogranins: metabolism
000167227 650_2 $$2MeSH$$aComputer Simulation
000167227 650_2 $$2MeSH$$aData Mining
000167227 650_2 $$2MeSH$$aDiabetes Mellitus, Type 1: genetics
000167227 650_2 $$2MeSH$$aDiabetes Mellitus, Type 1: metabolism
000167227 650_2 $$2MeSH$$aEpitopes
000167227 650_2 $$2MeSH$$aFemale
000167227 650_2 $$2MeSH$$aGene Expression Regulation
000167227 650_2 $$2MeSH$$aHLA-A3 Antigen
000167227 650_2 $$2MeSH$$aHumans
000167227 650_2 $$2MeSH$$aInsulin
000167227 650_2 $$2MeSH$$aMale
000167227 650_2 $$2MeSH$$aMice
000167227 650_2 $$2MeSH$$aMice, Inbred NOD
000167227 650_2 $$2MeSH$$aNeuroendocrine Secretory Protein 7B2: genetics
000167227 650_2 $$2MeSH$$aNeuroendocrine Secretory Protein 7B2: metabolism
000167227 650_2 $$2MeSH$$aProtein Binding
000167227 650_2 $$2MeSH$$aRNA, Messenger: genetics
000167227 650_2 $$2MeSH$$aUrocortins: genetics
000167227 650_2 $$2MeSH$$aUrocortins: metabolism
000167227 650_2 $$2MeSH$$aYoung Adult
000167227 7001_ $$aTarayrah, Mahmoud$$b1
000167227 7001_ $$aAfonso, Georgia$$b2
000167227 7001_ $$aPais, Aurore$$b3
000167227 7001_ $$aColli, Maikel L$$b4
000167227 7001_ $$aMaillard, Claire$$b5
000167227 7001_ $$aLavaud, Cassandra$$b6
000167227 7001_ $$00000-0002-4549-699X$$aAlexandre-Heymann, Laure$$b7
000167227 7001_ $$aGonzalez-Duque, Sergio$$b8
000167227 7001_ $$aVerdier, Yann$$b9
000167227 7001_ $$aVinh, Joelle$$b10
000167227 7001_ $$0P:(DE-He78)d2f9dbffa7b9a979f9bc4d81e769497e$$aPinto, Sheena$$b11
000167227 7001_ $$aBuus, Soren$$b12
000167227 7001_ $$00000-0003-3287-6309$$aDubois-Laforgue, Danièle$$b13
000167227 7001_ $$00000-0002-1017-1845$$aLarger, Etienne$$b14
000167227 7001_ $$aBeressi, Jean-Paul$$b15
000167227 7001_ $$aBruno, Graziella$$b16
000167227 7001_ $$00000-0003-2453-5889$$aEizirik, Decio L$$b17
000167227 7001_ $$aYou, Sylvaine$$b18
000167227 7001_ $$00000-0002-9846-8861$$aMallone, Roberto$$b19
000167227 773__ $$0PERI:(DE-600)1501252-9$$a10.2337/db20-0013$$gVol. 69, no. 12, p. 2678 - 2690$$n12$$p2678 - 2690$$tDiabetes$$v69$$x1939-327X$$y2020
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