The Third Way: Progress on pathways of antigen processing and presentation by CD1

CD1 proteins are a third family of antigen presenting molecules that bind bacterial and autologous lipid antigens for presentation to T cells. With the solution of the crystal structures of several complexes of CD1 molecules with lipids, a greater appreciation has been gained of the adaptability of CD1 in binding lipid antigens with diverse structural features. Biochemical studies of the interactions between the TCR and CD1-lipid complexes have revealed striking contrasts with TCR that bind to peptides presented by MHC-encoded class I and class II molecules. The sphingolipid activating proteins (SAP) have recently been found to facilitate the transfer of lipid antigens onto CD1 molecules. This helps to provide an explanation as to how the thermodynamic barrier, caused by loading hydrophobic lipid antigens in a hydrophilic environment, can be overcome. Mechanisms of CD1 endosomal trafficking are being delineated, including the means by which adaptor proteins induce the localization of some types of CD1 molecules to lysosomes, where they bind antigens. Unlike MHC class I and class II proteins, specialized molecules that function solely in chaperoning CD1 molecules, or in facilitating their antigen loading, have not been found. This suggests that the CD1 antigen presenting system, which diverged early in vertebrate evolution from MHC antigen presenting molecules, is a simpler system with a character closer to the primordial antigen presenting function.