The DOI matches its Crossref record; 57 of the 58 references it cites were found in a registry or an index.
Cardiolipin Binds to CD1d and Stimulates CD1d-Restricted γδ T Cells in the Normal Murine Repertoire
Open accessAbstract
Cardiolipin (CL), a major phospholipid in bacterial cell walls, is sequestered from the immune system in mammalian mitochondria and is, therefore, a potential danger signal. Based on growing evidence that phospholipids constitute natural ligands for CD1 and that CD1d-restricted T cells recognize phospholipids, we hypothesized that CD1d binds and presents CL and that T cells in the normal immune repertoire respond to CL in a CD1d-restricted manner. We determined the murine CD1d-CL crystal structure at 2.3 Å resolution and established through additional lipid loading experiments that CL, a tetra-acylated phospholipid, binds to murine CD1d with two alkyl chains buried inside the CD1d binding groove and the remaining two exposed into the solvent. We furthermore demonstrate the functional stimulatory activity of CL, showing that splenic and hepatic γδ T cells from healthy mice proliferate in vitro in response to mammalian or bacterial CL in a dose-dependent and CD1d-restricted manner, rapidly secreting the cytokines IFN-γ and RANTES. Finally, we show that hepatic γδ T cells are activated in vivo by CD1d-bearing dendritic cells that have been pulsed with CL, but not phosphatidylcholine. Together, these findings demonstrate that CD1d is able to bind and present CL to a subset of CL-responsive γδ T cells that exist in the spleen and liver of healthy mice and suggest that these cells could play a role in host responses to bacterial lipids and, potentially, self-CL. We propose that CL-responsive γδ T cells play a role in immune surveillance during infection and tissue injury.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Deletion of β2 microglobulin (an MHC class I molecule) or CD1d (a non-classical MHC protein) in an NZW/NZB F1 murine model of spontaneous SLE results in a reduction of circulating aCL antibodies223,224.”
From The role of mitochondria in rheumatic diseases (2022) · cites this paper as [224]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
[20] Processing of X-ray diffraction data collected in oscillation mode
Otwinowski, Z., & Minor, W. (1997) · Methods in Enzymology · doi:10.1016/s0076-6879(97)76066-x · Cited by 33,475
Coot : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571
The CCP4 suite: programs for protein crystallography
Number Collaborative Computational Project (1994) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444994003112 · Cited by 17,317
Refinement of Macromolecular Structures by the Maximum-Likelihood Method
Murshudov, G. N., Vagin, A. A., & Dodson, E. J. (1997) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444996012255 · Cited by 14,796
Electrostatics of nanosystems: Application to microtubules and the ribosome
Baker, N., Sept, D., Joseph, S., Holst, M., & McCammon, J. A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.181342398 · Cited by 7,125
PRODRG: a tool for high-throughput crystallography of protein–ligand complexes
Schüttelkopf, A. W., & van Aalten, D. M. F. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904011679 · Cited by 4,837
MOLREP : an Automated Program for Molecular Replacement
Vagin, A. A., & Teplyakov, A. (1997) · Journal of Applied Crystallography · doi:10.1107/s0021889897006766 · Cited by 4,756
Structure validation by Cα geometry: ϕ,ψ and Cβ deviation
Lovell, S. C., Davis, I. W., Arendall, W. B., de Bakker, P. I. W., Word, J. M., Prisant, M. G., Richardson, J. S., & Richardson, D. C. (2003) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.10286 · Cited by 4,595
Free R value: a novel statistical quantity for assessing the accuracy of crystal structures
Brünger, A. T. (1992) · Nature · doi:10.1038/355472a0 · Cited by 3,877
PDB2PQR: an automated pipeline for the setup of Poisson-Boltzmann electrostatics calculations
Dolinsky, T. J., Nielsen, J. E., McCammon, J. A., & Baker, N. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh381 · Cited by 3,517
CD1d-Restricted and TCR-Mediated Activation of V α 14 NKT Cells by Glycosylceramides
Kawano, T., Cui, J., Koezuka, Y., Toura, I., Kaneko, Y., Motoki, K., Ueno, H., Nakagawa, R., Sato, H., Kondo, E., et al. (1997) · Science · doi:10.1126/science.278.5343.1626 · Cited by 2,400
Bendelac, A. S., Savage, P. B., & Teyton, L. (2006) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141711 · Cited by 2,169
Use of TLS parameters to model anisotropic displacements in macromolecular refinement
Winn, M., Isupov, M. N., & Murshudov, G. N. (2001) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444900014736 · Cited by 1,685
Levine, J. S., Branch, D. W., & Rauch, J. (2002) · New England Journal of Medicine · doi:10.1056/nejmra002974 · Cited by 1,524
Self-citationRecognition of a lipid antigen by CD1-restricted αβ+ T cells
Beckman, E. M., Porcelli, S. A., Morita, C. T., Behar, S. M., Furlong, S. T., & Brenner, M. B. (1994) · Nature · doi:10.1038/372691a0 · Cited by 977
Self-citationTracking the Response of Natural Killer T Cells to a Glycolipid Antigen Using Cd1d Tetramers
Matsuda, J. L., Naidenko, O. V., Gapin, L., Nakayama, T., Taniguchi, M., Wang, C.-R., Koezuka, Y., & Kronenberg, M. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.5.741 · Cited by 887
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
Intravascular Immune Surveillance by CXCR6+ NKT Cells Patrolling Liver Sinusoids
Geissmann, F., Cameron, T. O., Sidobre, S., Manlongat, N., Kronenberg, M., Briskin, M., Dustin, M. L., & Littman, D. R. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030113 · Cited by 681
RANTES: a versatile and controversial chemokine
Appay, V., & Rowland‐Jones, S. (2001) · Trends in Immunology · doi:10.1016/s1471-4906(00)01812-3 · Cited by 652
Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria
Kinjo, Y., Tupin, E., Wu, D., Fujio, M., García‐Navarro, R., Benhnia, M. R., Zajonc, D. M., Ben‐Menachem, G., Ainge, G. D., Painter, G. F., et al. (2006) · Nature Immunology · doi:10.1038/ni1380 · Cited by 640
Self-citationMurine CD1d-Restricted T Cell Recognition of Cellular Lipids
Gumperz, J. E., Roy, C. J., Makowska, A., Lum, D. A., Sugita, M., Podrebarac, T., Koezuka, Y., Porcelli, S. A., Cardell, S., Brenner, M. B., et al. (2000) · Immunity · doi:10.1016/s1074-7613(00)80174-0 · Cited by 469
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
Jahng, A., Maricic, I., Aguilera, C., Cardell, S., Halder, R. C., & Kumar, V. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20031389 · Cited by 410
Schlame, M. (2008) · Journal of Lipid Research · doi:10.1194/jlr.r700018-jlr200 · Cited by 388
Tissue-Specific Segregation of CD1d-Dependent and CD1d-Independent NK T Cells
Eberl, G., Lees, R. K., Smiley, S. T., Taniguchi, M., Grusby, M. J., & MacDonald, H. R. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.11.6410 · Cited by 324
Structure and function of a potent agonist for the semi-invariant natural killer T cell receptor
Zajonc, D. M., Cantu, C., Mattner, J., Zhou, D., Savage, P. B., Bendelac, A. S., Wilson, I. A., & Teyton, L. (2005) · Nature Immunology · doi:10.1038/ni1224 · Cited by 309
Self-citationRecognition of Lyso-Phospholipids by Human Natural Killer T Lymphocytes
Fox, L. M., Cox, D. G., Lockridge, J. L., Wang, X., Chen, X., Scharf, L., Trott, D. L., Ndonye, R. M., Veerapen, N., Besra, G. S., et al. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000228 · Cited by 238
CD1.1 Expression by Mouse Antigen-Presenting Cells and Marginal Zone B Cells
Roark, J. H., Park, S., Jayawardena, J., Kavita, U., Shannon, M., & Bendelac, A. S. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.7.3121 · Cited by 232
Human CD1-restricted T cell recognition of lipids from pollens
Agea, E., Russano, A. M., Bistoni, O., Mannucci, R., Nicoletti, I., Corazzi, L., Postle, A. D., Libero, G. D., Porcelli, S. A., & Spinozzi, F. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050773 · Cited by 230
Zajonc, D. M., Maricic, I., Wu, D., Halder, R. C., Roy, K. C., Wong, C., Kumar, V., & Wilson, I. A. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20051625 · Cited by 192
Self-citationDetermination of Cellular Lipids Bound to Human CD1d Molecules
Cox, D., Fox, L. M., Tian, R., Bardet, W., Skaley, M. S., Mojsilovic, D., Gumperz, J. E., & Hildebrand, W. H. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005325 · Cited by 154
Innate immune functions of human γδ T cells
Beetz, S., Wesch, D., Marischen, L., Welte, S., Oberg, H., & Kabelitz, D. (2007) · Immunobiology · doi:10.1016/j.imbio.2007.10.006 · Cited by 144
Inflammation-associated lysophospholipids as ligands for CD1d-restricted T cells in human cancer
Chang, D., Deng, H., Matthews, P., Krasovsky, J., Ragupathi, G., Špíšek, R., Mazumder, A., Vesole, D. H., Jagannath, S., & Dhodapkar, M. V. (2008) · Blood · doi:10.1182/blood-2008-04-149831 · Cited by 143
Wu, D., Zajonc, D. M., Fujio, M., Sullivan, B. A., Kinjo, Y., Kronenberg, M., Wilson, I. A., & Wong, C. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600285103 · Cited by 137
Self-citationRauch, J., Gumperz, J. E., Robinson, C., Sköld, M., Roy, C., Young, D. C., Lafleur, M., Moody, D. B., Brenner, M. B., Costello, C. E., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308089200 · Cited by 135
Self-citationGiabbai, B., Sidobre, S., Crispin, M., Sánchez-Ruíz, Y., Bachi, A., Kronenberg, M., Wilson, I. A., & Degano, M. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.2.977 · Cited by 123
Multiple tissue‐specific isoforms of sulfatide activate CD1d‐restricted type II NKT cells
Blomqvist, M., Rhost, S., Teneberg, S., Löfbom, L., Østerbye, T., Brigl, M., Månsson, J., & Cardell, S. (2009) · European Journal of Immunology · doi:10.1002/eji.200839001 · Cited by 113
Transient increase in circulating gamma/delta T cells during Plasmodium vivax malarial paroxysms.
Perera, M. K. T., Carter, R., Goonewardene, R., & Mendis, K. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.179.1.311 · Cited by 113
Toward a Definition of Self: Proteomic Evaluation of the Class I Peptide Repertoire
Hickman, H. D., Luis, A. D., Buchli, R., Few, S. R., Sathiamurthy, M., VanGundy, R. S., Giberson, C. F., & Hildebrand, W. H. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.5.2944 · Cited by 110
Howlin, B. J., Butler, S. A., Moss, D. S., Harris, G. W., & DRIESSEN, H. P. C. (1993) · Journal of Applied Crystallography · doi:10.1107/s0021889893002729 · Cited by 101
Zajonc, D. M., Savage, P. B., Bendelac, A. S., Wilson, I. A., & Teyton, L. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.01.061 · Cited by 98
Self-citationWang, J., Li, Y., Kinjo, Y., Mac, T.-T., Gibson, D., Painter, G. F., Kronenberg, M., & Zajonc, D. M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909479107 · Cited by 95
Self-citationGlycolipids and phospholipids as natural CD1d-binding NKT cell ligands
Tsuji, M. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-006-6073-z · Cited by 95
Recognition of pollen-derived phosphatidyl-ethanolamine by human CD1d-restricted γδ T cells
Russano, A. M., Agea, E., Corazzi, L., Postle, A. D., Libero, G. D., Porcelli, S. A., Benedictis, F. M. D., & Spinozzi, F. (2006) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2006.01.001 · Cited by 89
Role of CD1d in Coxsackievirus B3-Induced Myocarditis
Huber, S. A., Sartini, D., & Exley, M. A. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.6.3147 · Cited by 88
CD1-Restricted Recognition of Exogenous and Self-Lipid Antigens by Duodenal γδ+ T Lymphocytes
Russano, A. M., Bassotti, G., Agea, E., Bistoni, O., Mazzocchi, A., Morelli, A., Porcelli, S. A., & Spinozzi, F. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.6.3620 · Cited by 81
Innate immune response to encephalomyocarditis virus infection mediated by CD1d
Exley, M. A., Bigley, N. J., Cheng, O., Shaulov, A., Tahir, S. M., Carter, Q. L., García, J. A., Wang, C., Patten, K., Stills, H. F., et al. (2003) · Immunology · doi:10.1111/j.1365-2567.2003.01779.x · Cited by 80
Structural Characterization of Mycobacterial Phosphatidylinositol Mannoside Binding to Mouse CD1d
Zajonc, D. M., Ainge, G. D., Painter, G. F., Severn, W. B., & Wilson, I. A. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.7.4577 · Cited by 75
Self-citationImmunology of the gut and liver: a love/hate relationship
Adams, D., Eksteen, B., & Curbishley, S. M. (2008) · Gut · doi:10.1136/gut.2007.122168 · Cited by 71
CD1 mediated T cell recognition of glycolipids
Zajonc, D. M., & Kronenberg, M. (2007) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2007.09.010 · Cited by 56
Self-citationγδ T Lymphocytes—Selectable Cells Within the Innate System?
Born, W. K., Jin, N., Aydintug, M. K., Wands, J. M., French, J. D., Roark, C. L., & O’Brien, R. L. (2007) · Journal of Clinical Immunology · doi:10.1007/s10875-007-9077-z · Cited by 48
Oliaro, J., Dudal, S., Liautard, J., Andrault, J.-B., Liautard, J., & Lafont, V. (2005) · Journal of Leukocyte Biology · doi:10.1189/jlb.0704433 · Cited by 43
Zajonc, D. M., & Wilson, I. A. (2007) · Springer eBooks · doi:10.1007/978-3-540-69511-0_2 · Cited by 40
Self-citationNatural T, γδ, and NK Cells in Mycobacterial,Salmonella,and Human Immunodeficiency Virus Infections
Jason, J. M., Buchanan, I., Archibald, L. K., Nwanyanwu, O. C., Bell, M. R., Green, T. A., Eick, A. A., Han, A., Razsi, D., Kazembe, P. N., et al. (2000) · The Journal of Infectious Diseases · doi:10.1086/315740 · Cited by 38
Born, W. K., Vollmer, M., Reardon, C. L., Matsuura, E., Voelker, D. R., Giclas, P. C., & O’Brien, R. L. (2003) · Scandinavian Journal of Immunology · doi:10.1046/j.1365-3083.2003.01315.x · Cited by 36
Human V 2V 2 T cells contain cytoplasmic RANTES
Tikhonov, I. I. (2006) · International Immunology · doi:10.1093/intimm/dxl055 · Cited by 24
Gamma delta T cells in infectious diseases.
Paoli, P. D., Basaglia, G., Gennari, D., & Santini, G. (1991) · PubMed · Cited by 4
Flagged first, then by citations
1 of the 58 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- de Paoli, 1991, γ δ T cells in infectious diseases, Allergol. Immunopathol. (Madr.), 19, 123
Cited by
Sorted by citations
Mitochondrial control of inflammation
Marchi, S., Guilbaud, E., Tait, S. W. G., Yamazaki, T., & Galluzzi, L. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-022-00760-x · Cited by 1,027
Mitochondria: master regulators of danger signalling
Galluzzi, L., Kepp, O., & Kroemer, G. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3479 · Cited by 733
γδ T Cells: First Line of Defense and Beyond
Chien, Y., Meyer, C., & Bonneville, M. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120216 · Cited by 669
Linking cellular stress responses to systemic homeostasis
Galluzzi, L., Yamazaki, T., & Kroemer, G. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0068-0 · Cited by 556
Mitochondrial Damage-Associated Molecular Patterns: From Inflammatory Signaling to Human Diseases
Grazioli, S., & Pugin, J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00832 · Cited by 429
Metadata
- Authors
- Dieudé, M., Striegl, H., Tyznik, A. J., Wang, J., Behar, S. M., Piccirillo, C. A., Levine, J. S., Zajonc, D. M., & Rauch, J.
- Affiliations
- Research Institute of the McGill University Health Centre (CA)
- La Jolla Institute for Immunology (US)
- Brigham and Women's Hospital (US)
- McGill University (CA)
- University of Illinois Chicago (US)
- Corresponding author
- Rauch, Joyce
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-04
- Volume
- 186
- Issue
- 8
- Pages
- 4771-4781
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC3076096
- OpenAlex
- W2150433277
- Cited by
- 121
- References
- 58
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 9 · 2023: 8 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 7 · 2018: 14 · 2017: 7 · 2016: 9 · 2015: 13 · 2014: 9 · 2013: 8 · 2012: 8
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Cancer Research Institute
- McGill University
- McGill University Health Centre
- National Institutes of Health
- Canadian Institutes of Health Research (97916, 67101, MOP-67101, MOP-42391)
- National Heart, Lung, and Blood Institute (R01HL080330, HL080330)
- National Institute of Allergy and Infectious Diseases (F32AI080087, R01AI074952, F32 AI 80087, AI074952, R56AI074952)
- Institute of Musculoskeletal Health and Arthritis
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- cardiolipin, CD1d, damage-associated molecular patterns, lipid ligands, interferon-gamma, RANTES, dendritic cells, bacterial lipids, immune surveillance, autoantigens
- MeSH terms
- Animals, Binding Sites, Cardiolipins, Crystallization, Female, Flow Cytometry, Interferon-gamma, Liver, Lymphocyte Activation, Male, Mice, Inbred C57BL, Models, Molecular, Protein Binding, Spleen, T-Lymphocytes, X-Ray Diffraction, Molecular Structure, Receptors, Antigen, T-Cell, gamma-delta, Protein Structure, Tertiary, Antigen Presentation, Mice, Knockout, Chemokine CCL5, Cell Proliferation, Mice, Antigens, CD1d
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
