Cel 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. Dziedzina nauki medical and health sciencesbasic medicineimmunologyimmunisationmedical and health sciencesclinical medicinepneumologytuberculosismedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccinesmedical and health sciencesbasic medicineimmunologyimmunotherapynatural sciencesbiological sciencesgeneticsgenomes Słowa kluczowe Vaccine Tuberculosis TB Program(-y) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Temat(-y) 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 Zaproszenie do składania wniosków FP6-2003-LIFESCIHEALTH-3 Zobacz inne projekty w ramach tego zaproszenia System finansowania STREP - Specific Targeted Research Project Koordynator DANMARKS TEKNISKE UNIVERSITET Wkład UE Brak danych Adres Anker Engelunds Vej 1 KGS. LYNGBY Dania Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych Uczestnicy (3) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko GANYMED PHARMACEUTICALS AKTIENGESELLSCHAFT Niemcy Wkład UE Brak danych Adres Freiligrathstrasse 12 MAINZ Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych KØBENHAVNS UNIVERSITET Dania Wkład UE Brak danych Adres Nørregade 10 COPENHAGEN Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych LEIDEN UNIVERSITY MEDICAL CENTER Niderlandy Wkład UE Brak danych Adres Albinusdreef 2 9600 LEIDEN Zobacz na mapie Linki Strona internetowa Opens in new window Koszt całkowity Brak danych