- 专利标题: ANTIGENIC PEPTIDES DERIVING FROM PCSK2 AND USES THEREOF FOR THE DIAGNOSIS AND TREATMENT OF TYPE 1 DIABETES
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申请号: US16981462申请日: 2019-03-15
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公开(公告)号: US20210023209A1公开(公告)日: 2021-01-28
- 发明人: Roberto MALLONE , Yann VERDIER , Joëlle VINH , Marie-Eliane AZOURY , Sergio GONZALEZ-DUQUE , Georgia AFONSO
- 申请人: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) , UNIVERSITE DE PARIS , CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) , ECOLE SUPERIEURE DE PHYSIQUE ET DE CHIMIE INDUSTRIELLES DE LA VILLE DE PARIS
- 申请人地址: FR Paris; FR Paris; FR Paris; FR Paris
- 专利权人: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE),UNIVERSITE DE PARIS,CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS),ECOLE SUPERIEURE DE PHYSIQUE ET DE CHIMIE INDUSTRIELLES DE LA VILLE DE PARIS
- 当前专利权人: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE),UNIVERSITE DE PARIS,CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS),ECOLE SUPERIEURE DE PHYSIQUE ET DE CHIMIE INDUSTRIELLES DE LA VILLE DE PARIS
- 当前专利权人地址: FR Paris; FR Paris; FR Paris; FR Paris
- 优先权: EP18305287.7 20180316
- 国际申请: PCT/EP2019/056540 WO 20190315
- 主分类号: A61K39/395
- IPC分类号: A61K39/395 ; C07K14/47 ; C07K14/725 ; C12N15/115 ; C12N15/62
摘要:
Despite the notion that human CD8+ T cells are the final mediators of autoimmune β-cell destruction in type 1 diabetes (T1D), none of their target epitopes has been demonstrated to be naturally processed and presented by β cells. The inventors therefore performed an epitope discovery study combining HLA Class I peptidomics and transcriptomics strategies. Inflammatory cytokines increased β-cell peptide presentation in vitro, paralleling upregulation of HLA Class I expression. Peptide sources included known β-cell antigens and several insulin granule proteins. PCSK2 was identified as a novel β-cell antigen, which was processed into HLA-A2-restricted epitopes recognized by circulating naïve CD8+ T cells in type 1 diabetic and healthy donors. Accordingly, the present invention relates to antigenic peptides derived from PCSK2 and uses thereof for the diagnosis and treatment of T1D.
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