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Saposins utilize two strategies for lipid transfer and CD1 antigen presentation
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Orientador(es)
Resumo(s)
Transferring lipid antigens from membranes into CD1 antigen-presenting proteins represents a major molecular hurdle necessary for T-cell recognition. Saposins facilitate this process, but the mechanisms used are not well understood. We found that saposin B forms soluble saposin protein-lipid complexes detected by native gel electrophoresis that can directly load CD1 proteins. Because saposin B must bind lipids directly to function, we found it could not accommodate long acyl chain containing lipids. In contrast, saposin C facilitates CD1 lipid loading in a different way. It uses a stable, membrane-associated topology and was capable of loading lipid antigens without forming soluble saposin-lipid antigen complexes. These findings reveal how saposins use different strategies to facilitate transfer of structurally diverse lipid antigens.
Descrição
Funding: We are grateful to A.N. Odyniec, M. Brigl, G.F.M. Watts, and T.Y. Cheng for suggestions and excellent technical assistance. This work was supported by National Institutes of Health (NIH) Grants AI028973 and AI063428 (to M.B.B.), DK36729 and NS36681 (to G.A.G.), and AR048632 and AI049313 (to D.B.M. and A.K.); a Howard Hughes Medical Institute Gilliam Fellowship (to L.L.); the Burroughs Wellcome Fund (D.B.M. and A.K.); a Personal Research Chair from Mr. James Bardrick (to V.B., N.V., and G.S.B.); a Royal Society Wolfson Research Merit Award (to V.B., N.V., and G.S.B.); the Medical Research Council (V.B., N.V., and G.S.B.); Wellcome Trust Grant 084923/B/08/Z (to V.B., N.V., and G.S.B.); and a Netherlands Organization for Scientific Research Grant (to A.J.M.
Palavras-chave
Natural Killer T cell tuberculosis immunogenicity lipid binding protein T-CELL RECOGNITION MYCOBACTERIUM-TUBERCULOSIS LYSOSOMAL DEGRADATION BETA-GLUCOSIDASE MHC-II BINDING GLUCOSYLCERAMIDASE PROTEINS RECONSTITUTION PHOSPHOLIPIDS SDG 3 - Good Health and Well-being