NKT cells constitute a T cell specific population characterized by the expression of the NK1.1 recptor of Natural Killer cells and an invariant TCR V\alpha chain, both in mouse and human (V\alpha14J\alpha15 yV\alpha24Q\alpha, respectively). This restricted receptor is specifically designed by nature to recognize CD1d, the only CD1 isotype found in all species analyzed todate. The CD1 family, which is structurally and functionaly related to MHC presenting molecules, specializes in presenting glycolipids to antigen specific T cells. The CD1d isotype has an unique functionality in the inmune system as it is recognized in an autoreactive way by NKT cells, being this modulated by endogenous glycolipids bound in endocytic compartments. NKT cells respond to CD1d+cells by secreting Th1 and Th2 type interleukines whose ratio, which depends either on the nature of endogenous ligands or on environmental conditions, regulates the inmune response of the organism with special implications in autoinmune responses. Due to its tyrosine motif inthe cytoplasmic tail that regulates intracellular traffic, CD1d is internalized to the more mature compartaments of the endocytic system, where processed endogenous glycolipids recognized by NKT cells are presumably bound. We aim to characterize the specificity of the NKT recognition at the molecular level, both in the direct interaction with CD1d and in its putative modulation by the endogenous ligands constitutively presented by CD1d. To do this analysis, we will generate a set of CD1d molecules that preferibly localize to the different compartments of the endocytic route, similary to the natural distribution of group I isotypes, to determine their differential recognition by NKT clones. In this way, we will analyze both the implication of endogenous ligands in the autoreactive recognition and the compartments involved in the generation and binding of the ligands, and also the diversity of the NKT response.
|Effective start/end date||1/12/02 → 1/12/05|