Obiettivo Vaccines against tuberculosis are urgently needed (Jordan Report, 2000). CD4 T cell responses play a major role in the generation of acquired immunity against M.tubercolosis. However, it is increasingly recognised that CD8 cytotoxic T cells (CTL) also con tribute to optimal host defence against mycobacteria. Of the various CTL subsets, it is commonly accepted that the conventional MHC-Ia restricted CD8 T cell subset play a major role. Unfortunately, relatively few CTL responses against TB have been identif ied. The object of this proposal is to perform a complete antigen-and epitope- discovery of relevance for human immune CTL responses against M.tuberculosis. Focusing on HLA class I restricted CTL constitutes the major risk involved in this project. To mee t our global objectives within the limited time and resources available for this project, we will combine several recently established innovative high-throughput methods from immunology and bioinformatics. Two different screening approaches will be used; o ne of "Forward Antigen Discovery", where expression libaries representing the whole M.tuberculosis genome is screened for proteins that are target for CTL repsonses in TB patients, and one of "Reverse Antigen Discovery", where proteins, which are likely to contain CTL epitopes, are predicted using computational methods, pre- validated by binding to relevant HLA molecules, and finally validated using CTL response from TB patients. The strategy will be initially to perform a genome-wide identification of nove l target proteins. Within these proteins we will subsequently perform HLA-wide epitope discovery where epitopes restricted by one of the major HLA supertypes are predicted, pre- validated for HLA binding and tested for CTL responses in TB patients.Our gene ral goal is to generate a European genomics/proteomics based platform for antigen and epitope discovery, and specifically to test it in the development of vaccines and immunotherapy. Campo scientifico medical and health sciencesbasic medicineimmunologyimmunisationmedical and health sciencesclinical medicinepneumologytuberculosismedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccinesmedical and health sciencesbasic medicineimmunologyimmunotherapynatural sciencesbiological sciencesgeneticsgenomes Parole chiave Vaccine Tuberculosis TB Programma(i) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Argomento(i) LIFESCIHEALTH-1.1.1 - Gene expression and proteomics LSH-2003-2.3.0-1 - Highly innovative approaches for the development of new interventions for HIV, malaria and tuberculosis Invito a presentare proposte FP6-2003-LIFESCIHEALTH-3 Vedi altri progetti per questo bando Meccanismo di finanziamento STREP - Specific Targeted Research Project Coordinatore DANMARKS TEKNISKE UNIVERSITET Contributo UE Nessun dato Indirizzo Anker Engelunds Vej 1 KGS. LYNGBY Danimarca Mostra sulla mappa Collegamenti Sito web Opens in new window Costo totale Nessun dato Partecipanti (3) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto GANYMED PHARMACEUTICALS AKTIENGESELLSCHAFT Germania Contributo UE Nessun dato Indirizzo Freiligrathstrasse 12 MAINZ Mostra sulla mappa Collegamenti Sito web Opens in new window Costo totale Nessun dato KØBENHAVNS UNIVERSITET Danimarca Contributo UE Nessun dato Indirizzo Nørregade 10 COPENHAGEN Mostra sulla mappa Collegamenti Sito web Opens in new window Costo totale Nessun dato LEIDEN UNIVERSITY MEDICAL CENTER Paesi Bassi Contributo UE Nessun dato Indirizzo Albinusdreef 2 9600 LEIDEN Mostra sulla mappa Collegamenti Sito web Opens in new window Costo totale Nessun dato
