The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
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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Cites
CD1-Restricted T Cell Recognition of Microbial Lipoglycan Antigens
Sieling, P. A., Chatterjee, D., Porcelli, S. A., Prigozy, T. I., Mazzaccaro, R. J., Soriano, T. T., Bloom, B. R., Brenner, M. B., Kronenberg, M., Brennan, P. J., et al. (1995) · Science · doi:10.1126/science.7542404 · Cited by 727
Self-citationTHE CD1 SYSTEM: Antigen-Presenting Molecules for T Cell Recognition of Lipids and Glycolipids
Porcelli, S. A., & Modlin, R. L. (1999) · Annual Review of Immunology · doi:10.1146/annurev.immunol.17.1.297 · Cited by 697
Self-citationRecognition of cluster of differentiation 1 antigens by human CD4−CD8>− cytolytic T lymphocyte
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Self-citationCD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection
Moody, D. B., Ulrichs, T., Mühlecker, W., Young, D. C., Gurcha, S. S., Grant, E. P., Rosat, J., Brenner, M. B., Costello, C. E., Besra, G. S., et al. (2000) · Nature · doi:10.1038/35009119 · Cited by 456
Self-citationStructural Requirements for Glycolipid Antigen Recognition by CD1b-Restricted T Cells
Moody, D. B., Reinhold, B. B., Guy, M. R., Beckman, E. M., Frederique, D. E., Furlong, S. T., Ye, S., Reinhold, V. N., Sieling, P. A., Modlin, R. L., et al. (1997) · Science · doi:10.1126/science.278.5336.283 · Cited by 441
Self-citationPrigozy, T. I., Sieling, P. A., Clemens, D., Stewart, P. L., Behar, S. M., Porcelli, S. A., Brenner, M. B., Modlin, R. L., & Kronenberg, M. (1997) · Immunity · doi:10.1016/s1074-7613(00)80425-2 · Cited by 337
Self-citationCalabi, F., Jarvis, J. M., Martin, L. H., & Milstein, C. (1989) · European Journal of Immunology · doi:10.1002/eji.1830190211 · Cited by 266
Structure of human CD1b with bound ligands at 2.3 Å, a maze for alkyl chains
Gadola, S. D., Zaccai, N. R., Harlos, K., Shepherd, D., Castro-Palomino, J. C., Ritter, G., Schmidt, R. R., Jones, E. Y., & Cerundolo, V. (2002) · Nature Immunology · doi:10.1038/ni821 · Cited by 259
Coding of Two Sphingolipid Activator Proteins (SAP-1 and SAP-2) by Same Genetic Locus
O’Brien, J. S., Kretz, K. A., Dewji, N. N., Wenger, D. A., Esch, F. S., & Fluharty, A. L. (1988) · Science · doi:10.1126/science.2842863 · Cited by 246
Is the development of a new tuberculosis vaccine possible?
Kaufmann, S. H. E. (2000) · Nature Medicine · doi:10.1038/79631 · Cited by 225
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The emerging field of lipidomics
Wenk, M. R. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1776 · Cited by 1,362
Macrophage defense mechanisms against intracellular bacteria
Weiss, G., & Schaible, U. E. (2015) · Immunological Reviews · doi:10.1111/imr.12266 · Cited by 989
Self-citationLysosomal Glycosphingolipid Recognition by NKT Cells
Zhou, D., Mattner, J., Cantu, C., Schrantz, N., Yin, N., Gao, Y., Sagiv, Y., Hudspeth, K., Wu, Y.-P., Yamashita, T., et al. (2004) · Science · doi:10.1126/science.1103440 · Cited by 956
Caseation of human tuberculosis granulomas correlates with elevated host lipid metabolism
Kim, M., Wainwright, H. C., Locketz, M., Bekker, L., Walther, G. B., Dittrich, C., Visser, A., Wang, W., Hsu, F., Wiehart, U., et al. (2010) · EMBO Molecular Medicine · doi:10.1002/emmm.201000079 · Cited by 489
Kolter, T., & Sandhoff, K. (2005) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.21.122303.120013 · Cited by 464
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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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