Saposins utilize two strategies for lipid transfer and CD1 antigen presentation

Luis Leon, Raju V. V. Tatituri, Rosa Grenha, Ying Sun, Duarte C. Barral, Adriaan J. Minnaard, Veemal Bhowruth, Natacha Veerapen, Gurdyal S. Besra, Anne Kasmar, Wei Peng, D. Branch Moody, Gregory A. Grabowski, Michael B. Brenner

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4357-4364
Number of pages8
JournalProceedings Of The National Academy Of Sciences Of The United States Of Ame
Volume109
Issue number12
DOIs
Publication statusPublished - 20 Mar 2012

Keywords

  • 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

Cite this

Leon, L., Tatituri, R. V. V., Grenha, R., Sun, Y., Barral, D. C., Minnaard, A. J., Bhowruth, V., Veerapen, N., Besra, G. S., Kasmar, A., Peng, W., Moody, D. B., Grabowski, G. A., & Brenner, M. B. (2012). Saposins utilize two strategies for lipid transfer and CD1 antigen presentation. Proceedings Of The National Academy Of Sciences Of The United States Of Ame, 109(12), 4357-4364. https://doi.org/10.1073/pnas.1200764109