CD1 proteins are distinguished by their ability to present lipid antigens to T cells. Group II CD1 or CD1d molecules are recognized by the specialized NK T-cell subset, and this reactivity can be greatly augmented by alpha-galactosylceramide, a glycosphingolipid derived from a marine sponge. Human CD1b, which is only distantly related to the CD1d molecules, can present mammalian glycosphingolipids (gangliosides) to autoreactive T-cell clones derived from multiple sclerosis patients. Thus, CD1 responsive and glycosphingolipid-reactive cells may play an important immune regulatory role, in addition to their well-characterized role in the response to microbial lipids.