Lipids are important antigens that induce T cell-mediated specific immune responses. They are presented to T cells by a class of MHC-I like proteins, namely CD1. Despite the highly diverse and abundant lipid content in the mycobacterial cell envelope, only a few of these lipids have been shown to stimulate CD1-restricted T cells. We previously described that some mycobacterial glycolipid antigens must be processed, however the underlying molecular mechanisms remain poorly defined. Altogether, lipid antigen properties make them attractive for their use in subunit vaccines against Mtb.
Our main working axes are:
- Characterization of the repertoire of mycobacterial lipid antigens involved in T cell responses.
- Functional and structural studies of CD1-lipid complexes, CD1 loading lipid mechanisms and investigation of specific recognition by the TCRs.
- Molecular mechanisms of lipid antigens processing: functional and structural studies of CD1e, definition of the repertoire of lipid-derived epitopes, characterization of lysosomal enzymatic activities involved in the generation of lipid epitopes.
- Evaluation of lipid neoantigen protective effect in animal models challenged with M. tuberculosis and proof-of-concept that CD1-restricted T cells can protect against mycobacterial infection.