Anatomy of CD1-lipid antigen complexes

CD1 proteins bind lipids to form antigen complexes that contact T-cell receptors and activate T cells. Recent crystal structures of CD1 proteins show that their antigen-binding grooves are composed of up to four pockets (A', C', F' and T') and two antigen portals ( C' and F'). Although certain structural features are conserved among CD1 proteins, the grooves of CD1a, CD1b and CD1d differ in the number, shape and connectivity of their antigen-binding pockets. Here, we outline how the portals and pockets of CD1 antigen-binding grooves influence ligand specificity and facilitate the presentation of a surprisingly diverse set of antigenic lipids, glycolipids, lipopeptides and even small, non-lipidic molecules.