Objective 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. Fields of science medical and health sciencesbasic medicineimmunologyimmunisationmedical and health sciencesclinical medicinepneumologytuberculosismedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccinesmedical and health sciencesbasic medicineimmunologyimmunotherapynatural sciencesbiological sciencesgeneticsgenomes Keywords Vaccine Tuberculosis TB Programme(s) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Topic(s) 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 Call for proposal FP6-2003-LIFESCIHEALTH-3 See other projects for this call Funding Scheme STREP - Specific Targeted Research Project Coordinator DANMARKS TEKNISKE UNIVERSITET EU contribution No data Address Anker Engelunds Vej 1 KGS. LYNGBY Denmark See on map Links Website Opens in new window Total cost No data Participants (3) Sort alphabetically Sort by EU Contribution Expand all Collapse all GANYMED PHARMACEUTICALS AKTIENGESELLSCHAFT Germany EU contribution No data Address Freiligrathstrasse 12 MAINZ See on map Links Website Opens in new window Total cost No data KØBENHAVNS UNIVERSITET Denmark EU contribution No data Address Nørregade 10 COPENHAGEN See on map Links Website Opens in new window Total cost No data LEIDEN UNIVERSITY MEDICAL CENTER Netherlands EU contribution No data Address Albinusdreef 2 9600 LEIDEN See on map Links Website Opens in new window Total cost No data
