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*
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232;
Department of Microbiology and Immunology, Indiana University School of Medicine, Walther Oncology Center, Indianapolis, IN 46202; and
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106
CD1d1 is a member of a family of lipid Ag-presenting molecules. The
cellular ligands associated with CD1d1 were isolated and characterized
by biochemical means as an approach to elucidate the mechanism by which
CD1 molecules assemble in vivo. Natural ligands of mouse CD1d1 included
cellular phosphatidylinositol and phosphatidylinositol-glycans that are
synthesized in the endoplasmic reticulum. Further biochemical data
revealed that the two CD1d1 mutants, one defective in recycling
from-and-to the plasma membrane and the other in efficiently
negotiating the secretory pathway, associated with
phosphatidylinositol. Thus phosphatidylinositol associated with CD1d1
in the early secretory pathway. Phosphatidylinositol also associated
with CD1d1 in Pig-A-deficient cells that are defective
in the first glycosylation step of glycosylphosphatidylinositol
biosynthesis. Moreover, cellular phosphatidylinositol-glycans are not
V
14J15 natural T cell Ags. Therefore, we predict that cellular
lipids occlude the hydrophobic Ag-binding groove of CD1 during assembly
until they are exchanged for a glycolipid Ag(s) within the recycling
compartment for display on the plasma membrane. In this manner,
cellular lipids might play a chaperone-like role in the assembly of
CD1d1 in vivo, akin to the function of invariant chain in MHC class II
assembly.
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