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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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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
Porcelli, S. A., Brenner, M. B., Greenstein, J. L., Terhorst, C., Balk, S. P., & Bleicher, P. A. (1989) · Nature · doi:10.1038/341447a0 · Cited by 530
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
Self-citationCytoplasmic Tail-Dependent Localization of CD1b Antigen-Presenting Molecules to MIICs
Sugita, M., Jackman, R. M., van Donselaar, E. G., Behar, S. M., Rogers, R. A., Peters, P. J., Brenner, M. B., & Porcelli, S. A. (1996) · Science · doi:10.1126/science.273.5273.349 · Cited by 222
Self-citationPresentation of the Same Glycolipid by Different CD1 Molecules
Shamshiev, A. T., Gober, H. J., Donda, A., Mazorra, Z., Mori, L., & Libero, G. D. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20011963 · Cited by 215
HARZER, K., Paton, B. C., Poulos, A., Kustermann‐Kuhn, B., Roggendorf, W., Grisar, T., & Popp, M. (1989) · European Journal of Pediatrics · doi:10.1007/bf02024331 · Cited by 199
Intracellular pathways of CD1 antigen presentation
Moody, D. B., & Porcelli, S. A. (2003) · Nature reviews. Immunology · doi:10.1038/nri979 · Cited by 194
Self-citationT-cell release of granulysin contributes to host defense in leprosy
Ochoa, M. T., Stenger, S., Sieling, P. A., Thoma-Uszynski, S., Sabet, S., Cho, S., Krensky, A. M., Röllinghoff, M., Sarno, E. N., Burdick, A. E., et al. (2001) · Nature Medicine · doi:10.1038/84620 · Cited by 174
Self-citationFailure of Trafficking and Antigen Presentation by CD1 in AP-3-Deficient Cells
Sugita, M., Cao, X., Watts, G. F. M., Rogers, R. A., Bonifacino, J. S., & Brenner, M. B. (2002) · Immunity · doi:10.1016/s1074-7613(02)00311-4 · Cited by 172
Self-citationLysosomal Degradation on Vesicular Membrane Surfaces
Wilkening, G., Linke, T. A., & Sandhoff, K. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.46.30271 · Cited by 156
Self-citationLipid length controls antigen entry into endosomal and nonendosomal pathways for CD1b presentation
Moody, D. B., Briken, V., Cheng, T., Roura‐Mir, C., Guy, M. R., Geho, D. H., Tykocinski, M. L., Besra, G. S., & Porcelli, S. A. (2002) · Nature Immunology · doi:10.1038/ni780 · Cited by 149
Self-citationSchnabel, D., Schröder, M., Fürst, W., Klein, A., HURWITZ, R. M., Zenk, T. S., Weber, J., HARZER, K., Paton, B. C., & Poulos, A. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)50733-5 · Cited by 148
Self-citationMoody, D. B., Guy, M. R., Grant, E. P., Cheng, T., Brenner, M. B., Besra, G. S., & Porcelli, S. A. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.7.965 · Cited by 148
Self-citationJackman, R. M., Stenger, S., Lee, A., Moody, D. B., Rogers, R. A., Niazi, K., Sugita, M., Modlin, R. L., Peters, P. J., & Porcelli, S. A. (1998) · Immunity · doi:10.1016/s1074-7613(00)80539-7 · Cited by 142
Self-citationSchaible, U. E., Hagens, K., Fischer, K., Collins, H., & Kaufmann, S. H. E. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.9.4843 · Cited by 117
Self-citationSaposins and Their Interaction with Lipids
Vaccaro, A. M., Salvioli, R., Tatti, M., & Ciaffoni, F. (1999) · Neurochemical Research · doi:10.1023/a:1022530508763 · Cited by 112
Vaccaro, A. M., Ciaffoni, F., Tatti, M., Salvioli, R., Barca, A., Tognozzi, D., & Scerch, C. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.51.30576 · Cited by 96
Intracellular trafficking pathway of newly synthesized CD1b molecules
Briken, V., Jackman, R. M., Dasgupta, S., Höning, S., & Porcelli, S. A. (2002) · The EMBO Journal · doi:10.1093/emboj/21.4.825 · Cited by 95
Self-citationSieling, P. A., Ochoa, M. T., Jullien, D., Leslie, D. S., Sabet, S., Rosat, J., Burdick, A. E., Rea, T. H., Brenner, M. B., Porcelli, S. A., et al. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.9.4790 · Cited by 89
Self-citationVielhaber, G., HURWITZ, R. M., & Sandhoff, K. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.50.32438 · Cited by 78
Self-citationInteraction of saposins, acidic lipids, and glucosylceramidase.
Morimoto, S., Kishimoto, Y., Tomich, J. M., Weiler, S., Ohashi, T., Barranger, J. A., Kretz, K. A., & O′Brien, J. S. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39921-1 · Cited by 76
Schuette, C. G., Pierstorff, B., Huettler, S., & Sandhoff, K. (2001) · Glycobiology · doi:10.1093/glycob/11.6.81r · Cited by 63
Self-citationEffect of Saposins A and C on the Enzymatic Hydrolysis of Liposomal Glucosylceramide
Vaccaro, A. M., Tatti, M., Ciaffoni, F., Salvioli, R., Barca, A., & Scerch, C. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.27.16862 · Cited by 60
Structure, function and biogenesis of the mycobacterial cell wall
Brennan, P. J., & Besra, G. S. (1997) · Biochemical Society Transactions · doi:10.1042/bst0250188 · Cited by 41
CD1-restricted antigen presentation: an oily matter
Joyce, S., & Kaer, L. V. (2003) · Current Opinion in Immunology · doi:10.1016/s0952-7915(02)00012-2 · Cited by 41
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Schaible, U. E., & Kaufmann, S. H. E. (2002) · Methods in microbiology · doi:10.1016/s0580-9517(02)31020-1 · Cited by 17
Self-citationStructural requirements for lysosomal targeting of the prosaposin precursor protein
Ham, D. (2003) · Cell Biology International · doi:10.1016/s1065-6995(03)00124-0 · Cited by 3
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Self-citation
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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