Mouse CD1 (mCD1) is an antigen-presenting molecule that is constitutively expressed by most bone marrow-derived cells. Peptides with a hydrophobic binding motif can bind to mCD1, and the peptide-CD1 complex is recognized by CD8+ cytolytic T cells. In contrast, NK1.1+ T cells, which are CD8-, are autoreactive for mCD1 molecules. This autoreactivity, along with the ability of NK T cells to rapidly produce large amounts of cytokine, has led to the suggestion that these cells may be immunoregulatory. We have shown that the mCD1-autoreactive T cells can distinguish between different cell types that express similar levels of mCD1, suggesting that mCD1-bound autologous ligands may be critical for T-cell stimulation. Consistent with this, some of these mCD1-restricted T cells can recognize the glycolipid alpha-galactosylceramide presented by mCD1, while others do not respond. The mCD1 crystal structure reveals a deep and narrow hydrophobic antigen-binding site which can more easily bind lipid antigens than the long hydrophobic peptides that we have defined as mCD1 antigens. The ability of mCD1 to bind and present two different types of ligands raises the question as to how mCD1 can accommodate both types of antigens.