Abstract: The present invention relates to methods and pharmaceutical compositions of inducing immune tolerance by mucosal vaccination with Fc-coupled antigens. In particular, the present invention relates to a method for inducing tolerance to one antigen of interest in a subject in need thereof, comprising the mucosal administration to the subject of a therapeutically effective amount of a recombinant chimeric construct comprising a FcRn targeting moiety and an antigen-containing moiety.

Abstract: The present invention relates to T-cell receptors (TCR) that recognize pancreatic betacell epitopes and uses thereof for the diagnosis and treatment of diabetes.

Abstract: Despite the notion that human CD8+ T cells are the final mediators of autoimmune ?-cell destruction in type 1 diabetes (TID), 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- 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.

Abstract: 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. Urocortin 3 was identified as a novel ?-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.

Abstract: 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. PCSK2 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. Accordingly, the present invention relates to antigenic peptides derived from PCSK2 and uses thereof for the diagnosis and treatment of T1D.

Abstract: The present invention relates to methods and pharmaceutical compositions of inducing immune tolerance by mucosal vaccination with Fc-coupled antigens. In particular, the present invention relates to a method for inducing tolerance to one antigen of interest in a subject in need thereof, comprising the mucosal administration to the subject of a therapeutically effective amount of a recombinant chimeric construct comprising a FcRn targeting moiety and an antigen-containing moiety.

Abstract: The present invention relates to methods and pharmaceutical compositions of inducing immune tolerance by mucosal vaccination with Fc-coupled antigens. In particular, the present invention relates to a method for inducing tolerance to one antigen of interest in a subject in need thereof, comprising the mucosal administration to the subject of a therapeutically effective amount of a recombinant chimeric construct comprising a FcRn targeting moiety and an antigen-containing moiety.

Abstract: The present invention relates to T-cell receptors (TCR) that recognize pancreatic betacell epitopes and uses thereof for the diagnosis and treatment of diabetes.

Abstract: The present invention relates to methods and pharmaceutical compositions of inducing immune tolerance by mucosal vaccination with Fc-coupled antigens. In particular, the present invention relates to a method for inducing tolerance to one antigen of interest in a subject in need thereof, comprising the mucosal administration to the subject of a therapeutically effective amount of a recombinant chimeric construct comprising a FcRn targeting moiety and an antigen-containing moiety.

Abstract: The present invention relates to methods for stimulating antigen-specific T cell responses. In particular, the invention relates to a method for stimulating antigen (Ag)-specific T cell responses in a blood sample or PBMC sample isolated from a subject comprising the step consisting in culturing said blood or PBMC sample in a appropriate culture medium which comprises an amount of IL-1beta and an amount of a least one antigen.

Abstract: Constructs and methods for inducing immune tolerance during gestation, e.g. in utero, are provided. The constructs comprise a moiety that targets and binds to the neonatal Fc receptor (FcRn) and a moiety comprising an antigen of interest for which immune tolerance is desired. Administration of the constructs to a fetus during gestation results in immune tolerance, e.g. to antigens that otherwise elicit an unwanted immune response such as an autoimmune reaction.

Abstract: The present invention relates to methods for testing T cell priming efficacy in a subject. In particular the present invention relates to an in vitro method for testing T cell priming efficacy in a subject comprising the steps of a) providing sample from the subject, b) culturing the sample in a medium which induces the differentiation of dendritic cells, c) maturing the dendritic cells obtained at step a) in presence of an amount of at least one antigen and an amount of at least one cytokine or ligand suitable for the activation of a pathogen recognition receptor, d) priming and expanding the T cells present in the sample and e) analyzing the func tionality of the primed T cells.

Abstract: The present invention relates to methods for stimulating antigen-specific T cell responses. In particular, the invention relates to a method for stimulating antigen (Ag)-specific T cell responses in a blood sample or PBMC sample isolated from a subject comprising the step consisting in culturing said blood or PBMC sample in a appropriate culture medium which comprises an amount of IL-1beta and an amount of a least one antigen.

Abstract: The invention relates to a method for stimulating antigen-specific T cell responses by using accelerated co-cultured dendritic cells, and to uses thereof, such as a method for diagnosing a disease and a method for producing isolated T cell clones displaying specific immunological properties.

Abstract: The present invention concerns antibodies recognizing Mycobacterium avium paratuberculosis epitopes able to cross-reacting with the beta-cell antigen ZnT8 to be used as early biomarkers of type 1 diabetes, epitopes for in vitro prognostic and diagnostic methods suitable to reveal a risk to develop type 1 diabetes, therapies for the prevention of T1D by avoiding, controlling or monitoring Mycobacterium paratuberculosis infection.

Abstract: The invention relates to a method for stimulating antigen-specific T cell responses by using accelerated co-cultured dendritic cells, and to uses thereof, such as a method for diagnosing a disease and a method for producing isolated T cell clones displaying specific immunological properties.