Linking lipid metabolism to immunity: The role of lipid transfer proteins in the selection of iNKT cells.
Extract: Since the emergence of the role that CD1d plays in selecting the natural killer T cell population expressing the semi-invariant V-alpha-14 T cell receptor (iNKT cells), a great deal of research has been done to identify the natural lipid antigen involved in this process. This interest has been sparked by the critical role of iNKT cells in the regulation of immune responses and their potential involvement in autoimmunity and the control of carcinogenesis. While iNKT cells show high autoreactivity, the only cellular lipid shown to be presented by CD1d has been phosphatidyl inositol, which does not activate iNKT cells by itself. The only lipid antigens known to activate iNKT cells have been alpha-glycosylceramides. However, alpha-galactosylceramide (alpha-GalCer) is derived from marine sponges and has no known equivalent in mammalian cells, which only synthesize beta-anomers of ceramide. Still, alpha-GalCer has proven to be a valuable tool in defining the role of iNKT cells in host defense, tumor immunity, and homeostatic regulation of anti-self responses. In order to discover the selecting lipid antigen(s), the road that CD1d travels to reach the cell surface and interact with iNKT cells required closer examination. Much work in recent years has shed light on the different pathways undertaken by the various members of the CD1 family to sample the various cellular compartments for lipid antigen presentation. In particular, trafficking of the CD1d molecule to the late endosomal and lysosomal compartments proved essential for selection of the iNKT cell population, suggesting that the natural lipid antigen(s) are sampled in these compartments.
Cantu
Carlos
C
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Teyton
Luc
L