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公开(公告)号：US20210023209A1
公开(公告)日：2021-01-28
申请号：US16981462
申请日：2019-03-15
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
发明人： Roberto MALLONE , Yann VERDIER , Joëlle VINH , Marie-Eliane AZOURY , Sergio GONZALEZ-DUQUE , Georgia AFONSO
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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公开(公告)号：US20210024603A1
公开(公告)日：2021-01-28
申请号：US16981474
申请日：2019-03-15
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
发明人： Roberto MALLONE , Sergio GONZALEZ-DUQUE , Yann VERDIER , Marie-Eliane AZOURY , Georgia AFONSO , Joëlle VINH
IPC分类号： C07K14/575 , C12N15/115 , C07K16/26 , C07K14/74
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. Urocortin 3 was identified as a novel β-cell antigen, which was processed into HLA-A2- and HLA-A3-restricted epitopes recognized by circulating naive CD8+ T cells in type 1 diabetic and healthy donors. Accordingly, the present invention relates to antigenic peptides derived from urocortin-3 and uses thereof for the diagnosis and treatment of T1D.
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公开(公告)号：US20210070819A1
公开(公告)日：2021-03-11
申请号：US16981352
申请日：2019-03-15
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 , Université Libre de Bruxelles
发明人： Roberto MALLONE , Joëlle VINH , Yann VERDIER , Decio LAKS EIZIRIK , Maikel Luis COLLI , Georgia AFONSO , Sergio GONZALEZ-DUQUE
摘要： Despite the notion that human CD8+ T cells are the final mediators of autoimmune β-cell destruction in type 1 diabetes (TID), 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. Secretogranin V (SCG5/7B2) was identified as a novel β-cell antigen, which was processed into HLA-A2- and HLA-A3-restricted epitopes recognized by circulating naïve CD8+ T cells in type 1 diabetic and healthy donors. HLA-A2-bound neo-epitopes were also represented and originated from an alternative SCG5-009 mRNA splice isoform. Accordingly, the present invention relates to antigenic peptides derived from secretogranin V and uses thereof for the diagnosis and treatment of T1D.
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公开(公告)号：US20230032690A1
公开(公告)日：2023-02-02
申请号：US17818481
申请日：2022-08-09
申请人： INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE) , UNIVERSITE DE LILLE , CENTRE HOSPITALIER REGIONAL UNIVERSITAIRE DE LILLE , CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) , ECOLE SUPERIEURE DE PHYSIQUE ET DE CHIMIE INDUSTRIELLES DE LA VILLE DE PARIS
发明人： Luc BUEE , Malika HAMDANE , David BLUM , Maxime DERISBOURG , Coline LEGHAY , Giovanni CHIAPPETTA , Joelle VINH , Yann VERDIER
摘要： The invention relates to the identification of a new Tau species starting at residue Met11 (Met11-Tau) which is N-alpha-terminally acetylated form (N-alpha-acetyl-Met11-Tau species: Ac-Met11-Tau). Several monoclonal antibodies specific of this new Tau species have been developed. One of this antibody, 2H2/D11, was used in THY-Tau22 mouse model (that develops with age neurofibrillary degeneration (NFD) and memory deficits), and N-alpha-Ac-Met11-Tau species were clearly detected early in neurons displaying NFD on hippocampal brain sections while it is not reactive in hippocampus from elderly controls. Finally, by using ELISA sandwich specific of Ac-Met11-Tau species, Alzheimer Disease (AD) brain samples are clearly discriminated from human elderly control brains. Thus the invention relates to this new Tau species starting from the methionine residue at position 11 said methionine being N-alpha acetylated. The invention also relates to antibody that specifically binds this new tau species, a method of detection of this new Tau species and a method of diagnosis of Tauopathy disorder.
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公开(公告)号：US20200031891A1
公开(公告)日：2020-01-30
申请号：US16498780
申请日：2018-03-27
申请人： INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE) , UNIVERSITE DE LILLE , CENTRE HOSPITALIER REGIONAL UNIVERSITAIRE DE LILLE , CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) , ECOLE SUPERIEURE DE PHYSIQUE ET DE CHIMIE INDUSTRIELLES DE LA VILLE DE PARIS
发明人： Luc BUEE , Malika HAMDANE , David BLUM , Maxime DERISBOURG , Coline LEGHAY , Giovanni CHIAPPETTA , Joelle VINH , Yann VERDIER
摘要： The invention relates to the identification of a new Tau species starting at residue Met11 (Met11-Tau) which is N-alpha-terminally acetylated form (N-alpha-acetyl-Met11-Tau species: Ac-Met11-Tau). Several monoclonal antibodies specific of this new Tau species have been developed. One of this antibody, 2H2/D11, was used in THY-Tau22 mouse model (that develops with age neurofibrillary degeneration (NFD) and memory deficits), and N-alpha-Ac-Met11-Tau species were clearly detected early in neurons displaying NFD on hippocampal brain sections while it is not reactive in hippocampus from elderly controls. Finally, by using ELISA sandwich specific of Ac-Met11-Tau species, Alzheimer Disease (AD) brain samples are clearly discriminated from human elderly control brains. Thus the invention relates to this new Tau species starting from the methionine residue at position 11 said methionine being N-alpha acetylated. The invention also relates to antibody that specifically binds this new tau species, a method of detection of this new Tau species and a method of diagnosis of Tauopathy disorder.
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