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Saposin C is required for lipid presentation by human CD1b
Abstract
Lipids from Mycobacterium tuberculosis are presented through CD1 proteins to T lymphocytes in humans, but the accessory molecules required for antigen loading and presentation remain unidentified. Here we show that fibroblasts deficient in sphingolipid activator proteins (SAPs) transfected with CD1b failed to activate lipid-specific T cells. However, the T cell response was restored when fibroblasts were reconstituted with SAP-C but not other SAPs. Lipid antigen and SAP-C colocalized in lysosomal compartments, and liposome assays showed that SAP-C efficiently extracts antigen from membranes. Coprecipitation demonstrated direct molecular interaction between SAP-C and CD1b. We propose a model in which SAP-C exposes lipid antigens from intralysosomal membranes for loading onto CD1b. Thus, SAP-C represents a missing link in antigen presentation of lipids through CD1b to human T cells.
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“Lysosomal lipid transfer proteins (LTPs), such as the four active saposins generated from pro-saposin by proteolytic cleavage, are essential for glyco-lipid degradation in lysosomes and glyco-lipid homeostasis, in addition to their immunologically relevant function in processing and presentation of lipid antigens by CD1b molecules in DC (41, 42).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [42]
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Metadata
- Authors
- Winau, F., Schwierzeck, V., Hurwitz, R., Remmel, N., Sieling, P. A., Modlin, R. L., Porcelli, S. A., Brinkmann, V., Sugita, M., Sandhoff, K., Kaufmann, S. H. E., & Schaible, U. E.
- Affiliations
- Max Planck Society (DE)
- University of California, Los Angeles (US)
- Albert Einstein College of Medicine (US)
- Nippon Medical School (JP)
- Corresponding author
- Kaufmann, Stefan H E
- ORCID
- Venue
- Nature Immunology
- Published
- 2004-01-11
- Volume
- 5
- Issue
- 2
- Pages
- 169-174
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2027841252
- Cited by
- 168
- References
- 34
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 5 · 2017: 5 · 2016: 6 · 2015: 9 · 2014: 6 · 2013: 4 · 2012: 9
- FWCI
- 7.21
- Type
- journal article
- Language
- en
- Update notices
- erratum (2004-03-01)
- Open access
- closed
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- saposin C, CD1b, lipid antigen presentation, Mycobacterium tuberculosis, sphingolipid activator proteins, antigen loading, T cell activation
- MeSH terms
- Antigen-Presenting Cells, beta-Glucosidase, Fibroblasts, Glycoproteins, Humans, Lipids, Lymphocyte Activation, Lysosomes, Protein Binding, T-Lymphocytes, Transfection, Antigen Presentation, Antigens, CD1, Sphingolipid Activator Proteins, Saposins, In Vitro Techniques
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