CRYSTAL-STRUCTURE OF MOUSE CD1 - AN MHC-LIKE FOLD WITH A LARGE HYDROPHOBIC BINDING GROOVE

CD1 represents a third lineage of antigen-presenting molecules that ar e distantly related to major histocompatibility complex (MHC) molecule s in the immune system. The crystal structure of mouse CD1d1, correspo nding to human CD1d, at 2.8 Angstrom resolution shows that CD1 adopts an MHC fold that is more closely related to that of MHC class I than t o that of MHC class II. The binding groove, although significantly nar rower, is substantially larger because of increased depth and it has o nly two major pockets that are almost completely hydrophobic. The extr eme hydrophobicity and shape of the binding site are consistent with o bservations that human CD1b and CD1c can present mycobacterial cell wa ll antigens, such as mycolic acid and lipoarabinomannans. However, mou se CD1d1 can present very hydrophobic peptides, but must do so in a ve ry different way from MHC class Ia and class II molecules.