Saposin B is the dominant saposin that facilitates lipid binding to human CD1d molecules

• DOI: 10.1073/pnas.0700617104
• Publication Date: 2007-03-20T00:36:00Z
• Authors: Weiming Yuan; Xiaoyang Qi; Pansy Tsang; Suk-Jo Kang; Petr A. Illarionov; Gurdyal S. Besra; Jenny Gumperz; Peter Cresswell
• Keywords: CD1D

CD1d molecules bind lipid antigens in the endocytic pathway, and access to pathway is important for development of CD1d-restricted natural killer T (NKT) cells. Saposins, derived from a common precursor, prosaposin, are small, heat-stable lysosomal glycoproteins required degradation sphingolipids. Expression prosaposin efficient binding recognition human by NKT Despite high sequence homology among four saposins, they have different specificities substrates mechanisms action. To determine saposins involved promoting CD1d, we expressed deletion mutants lacking individual prosaposin-negative, CD1d-positive No saposin proved be absolutely essential, but absence B resulted lowest α-galactosylceramide When recombinant exogenous were added prosaposin-negative cells, was most restoring recognition. Saposin also mediating plate-bound facilitating cell activation. could mediate soluble cell-independent assay. The optimal pH B-mediated 6, higher than that lysosomes, suggesting may facilitate throughout pathway.