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Genome- and HLA- Wide Scanning and Validation of Cytotoxic CD8 T Cell Responses against Mycobacterium Tuberculosis
Framework programme:
Project number:
EC contribution:
€ 1,053,445
24 months
Starting date:
1 January 2005

Keywords: Tuberculosis; vaccine; cellular immune response; CD8


Vaccines against tuberculosis are urgently needed. CD4 T cell responses play a major role in the generation of acquired immunity against M. tuberculosis. However, it is increasingly recognised that CD8 cytotoxic T cells (CTL) also contribute to optimal host defence against mycobacteria. Unfortunately, relatively few CTL responses against TB have been identified. The object of this proposal is to perform a complete antigen- and epitope- discovery of relevance for human immune CTL responses against M. tuberculosis. Several recently established innovative high-throughput methods from immunology and bioinformatics will be combined. Two different screening approaches will be used; one of ‘forward antigen discovery’, where expression libraries representing the whole M. tuberculosis genome will be screened for proteins that are targets for CTL responses 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 initially be to perform a genome-wide identification of novel 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.

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