Pathways for lipid antigen presentation by CD1 molecules: Nowhere for intracellular pathogens to hide

A crucial feature of peptide antigen presentation by major histocompatibilt y complex (MHC) class I and II molecules is their differential ability to s ample cytosolic and extracellular antigens. Intracellular viral infections and bacteria that are taken up in phagosomes, but then escape from the endo cytic compartment efficiently, enter the class I pathway via the cytosol. I n contrast. phagosome-resident bacteria yield protein antigens that are sam pled deep in the endocytic compartment and presented in a vacuolar acidific ation-dependent pathway mediated by MHC class II molecules. Despite this po tential for antigen sampling, microbes have evolved a variety of evasive me chanisms that affect peptide transport in the MHC class I pathway or blocka de of endosomal acidification and inhibition of phagosome-lysosome fusion t hat may compromise the MHC class II pathway of antigen presentation. Thus, besides MHC class I and II, a third lineage of antigen-presenting molecules that bind lipid and glycolipid antigens rather than peptides exists and is mediated by the family of CD1 proteins. CD1 isoforms (CD1a, b. c, and d) d ifferentially sample both recycling endosomes of the early endocytic system and late endosomes and lysosomes to which lipid antigens are differentiall y delivered. These CD1 pathways include vacuolar acidification-independent pathways for lipid antigen presentation. These features of presenting lipid antigens. independently monitoring various antigen-containing intracellula r compartments and avoiding certain evasive techniques employed by microbes , enable CD1 molecules to provide distinct opportunities to function in hos t defense against the microbial world.