Objetivo Insulin-dependent diabetes mellitus (IDDM, type I diabetes) is a metabolic autoimmune disease in humans in which the ß cells of the islets of Langerhans are selectively destroyed. To date, no cure has been developed for this disease. While it has been established that the destruction of this tissue predominantly occurs due to auto-reactive recognition by CD4 T cells, the etiology of this disease as well as many of the autoantigens recognized by these T cells, are unknown.Certain major histocompatibility com plex (MHC) class II alleles have been strongly linked with IDDM, such as DQ8 in humans and I-Ag7 in the non-obese diabetic (NOD) mouse, a spontaneous model for type I diabetes. In order to find a cure for IDDM, the target antigens that drive auto-reactive T cell recognition need to be identified and new immunotherapies need to be developed. Therefore, the main objectives of this project are the identification of one of these auto-antigens as well as the development of a novel DNA vaccine. To reach the first objective, several new in silico and in vitro approaches will be used for the identification of antigen candidates, that could possibly be recognized by a well characterized diabetogenic T cell clone called BDC2.5. Recombinant antigens will be generated in order to screen for the activation of BDC2.5.We will finally evaluate the natural T and B cell response against this autoantigen in vivo in the NOD mouse in order to assess the value of protein homologues for the development of new diagnostics for disease prediction in humans. The second objective will be the generation of a novel DNA vaccine coding for soluble I-Ag7/peptide dimers. We will use the BDC2.5 system as a model to explore its efficacy in the NOD mouse. I-Ag7/peptide tetramers will allow us to evaluate the specific T cell response quantitatively as well as qualitatively. These experiments will facilitate the design of equivalent vaccines for the prevention of IDDM in human patients. Ámbito científico natural sciencesbiological sciencesgeneticsDNAmedical and health sciencesclinical medicineendocrinologydiabetesmedical and health sciencesbasic medicineimmunologyautoimmune diseasesmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccinesmedical and health sciencesbasic medicineimmunologyimmunotherapy Palabras clave CD4 T cells DNA vaccine I-Ag7 MHC class II tetramers NOD mouse Type I diabetes autoantigens microarray Programa(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Tema(s) MOBILITY-4.2 - Marie Curie International Reintegration Grants (IRG) Convocatoria de propuestas FP6-2002-MOBILITY-12 Consulte otros proyectos de esta convocatoria Régimen de financiación IRG - Marie Curie actions-International re-integration grants Coordinador UNIVERSIDAD DE BARCELONA Aportación de la UE Sin datos Dirección Gran Via de les Corts Catalanes, 585 (Vicerectorat de Recerca; OPER) BARCELONA España Ver en el mapa Enlaces Sitio web Opens in new window Coste total Sin datos
