Antigenic peptides for the diagnosis and treatment of Type 1 Diabetes

Despite the notion that human CD8+ T cells are the final mediators of autoimmune ?-cell destruction in type 1 diabetes (T1D), none of their target epitopes has been demonstrated to be naturally processed and presented by ? cells. The inventors therefore performed an epitope discovery study combining HLA Class I peptidomics and transcriptomics strategies. Inflammatory cytokines increased ?-cell peptide presentation in vitro, paralleling upregulation of HLA Class I expression. Peptide sources included known ?-cell antigens and several insulin granule proteins. Secretogranin V (SCG5/7B2) was identified as a novel ?-cell antigen, which was processed into HLA-A2-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.

Patent Application number: European Procedure (Patents) (EPA) - 16 Mars 2018 - 18 305 286.9
Inventors:
MALLONE Roberto,GONZALEZ-DUQUE Sergio,VINH Joëlle,COLLI Maikel Luis,AFONSO Georgia,VERDIER Yann,LAKS EIZIRIK Decio

Reference:

BIO17382-D1

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Patent filling date: 2018-03-16

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