Saposins utilize two strategies for lipid transfer and CD1 antigen presentation

• Published in: Proceedings of the National Academy of Sciences - PNAS 2012-03, Vol.109 (12), p.4357-4364
• Main Authors: León, Luis, Tatituri, Raju V. V, Grenha, Rosa, Sun, Ying, Barral, Duarte C, Minnaard, Adriaan J, Bhowruth, Veemal, Veerapen, Natacha, Besra, Gurdyal S, Kasmar, Anne, Peng, Wei, Moody, D. Branch, Grabowski, Gregory A, Brenner, Michael B
• Format: Article
• Language: English
• Subjects: Animals; antigen presentation; Antigens; Antigens, CD1 - metabolism; Biological Sciences; CHO Cells; Cricetinae; Dimers; Electrophoresis, Agar Gel; Gangliosides; gel electrophoresis; Glycolipids - chemistry; Guanine nucleotide dissociation inhibitors; Humans; Hydrogen-Ion Concentration; Killer Cells, Natural - cytology; Lipid Bilayers - metabolism; Lipids; Lipids - chemistry; Liposomes; Liposomes - chemistry; Membranes; Models, Biological; Molecules; Proteins; Recombinant Proteins - chemistry; Saposins - chemistry; Saposins - physiology; T lymphocytes; T-Lymphocytes - cytology; Topology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1200764109

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.