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*
Department of Microbiology and Immunology and the Molecular Biology Institute, University of California at Los Angeles, Los Angeles, CA 90095;
Department of Medicine and Microbiology Immunology and Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, CA 93143; and
Department of Immunology, Department of Cellular and Molecular Biology, Lund University, Lund, Sweden
Humans and mice contain significant populations of T cells that are
reactive for autologous CD1 molecules. Using a panel of five mouse CD1
(mCD1)-autoreactive T cell hybridomas, we show here that this
autoreactivity does not correlate with the level of CD1 expression. In
some cases, these autoreactive T cells can distinguish between
different cell types that express the same CD1 molecule, suggesting
that some factor in addition to CD1 expression is critical for
autoreactive T cell stimulation. To determine whether a CD1-bound
ligand may be required, we expressed mutant mCD1 molecules that are
defective for the putative endosomal localization sequence in the
cytoplasmic domain. We demonstrate that mCD1, like its human CD1
homologues, is found in endosomes, and that it colocalizes extensively
with the DM molecule. We further demonstrate, by site-directed
mutagenesis, that the tyrosine in the cytoplasmic sequence is required
for this endosomal localization. A T cell hybrid expressing Vß8 and
V
14, the major TCR expressed by NK1+ T cells,
exhibited greatly diminished reactivity to mutant CD1 molecules that do
not traffic through endosomes, although the reactivity of other T cell
hybrids to this mutant was not greatly affected. Therefore, we propose
that at least some of the autoreactive T cells require endosomally
derived CD1-bound ligands, and that they are capable of distinguishing
between a diverse set of such self-ligands, which might be either
autologous lipoglycans or peptides.
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M. A. Exley, N. J. Bigley, O. Cheng, S. M. A. Tahir, S. T. Smiley, Q. L. Carter, H. F. Stills, M. J. Grusby, Y. Koezuka, M. Taniguchi, et al. CD1d-reactive T-cell activation leads to amelioration of disease caused by diabetogenic encephalomyocarditis virus J. Leukoc. Biol., May 1, 2001; 69(5): 713 - 718. [Abstract] [Full Text]
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 T. I. Prigozy, O. Naidenko, P. Qasba, D. Elewaut, L. Brossay, A. Khurana, T. Natori, Y. Koezuka, A. Kulkarni, and M. Kronenberg Glycolipid Antigen Processing for Presentation by CD1d Molecules Science, January 26, 2001; 291(5504): 664 - 667. [Abstract] [Full Text]
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A. Hameg, I. Apostolou, M. Leite-de-Moraes, J.-M. Gombert, C. Garcia, Y. Koezuka, J.-F. Bach, and A. Herbelin A Subset of NKT Cells That Lacks the NK1.1 Marker, Expresses CD1d Molecules, and Autopresents the {alpha}-Galactosylceramide Antigen J. Immunol., November 1, 2000; 165(9): 4917 - 4926. [Abstract] [Full Text] [PDF]
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J. L. Matsuda, O. V. Naidenko, L. Gapin, T. Nakayama, M. Taniguchi, C.-R. Wang, Y. Koezuka, and M. Kronenberg Tracking the Response of Natural Killer T Cells to a Glycolipid Antigen Using CD1d Tetramers J. Exp. Med., September 5, 2000; 192(5): 741 - 754. [Abstract] [Full Text] [PDF]
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I. Apostolou, A. Cumano, G. Gachelin, and P. Kourilsky Evidence for Two Subgroups of CD4-CD8- NKT Cells with Distinct TCR{alpha}{beta} Repertoires and Differential Distribution in Lymphoid Tissues J. Immunol., September 1, 2000; 165(5): 2481 - 2490. [Abstract] [Full Text] [PDF]
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N. Burdin, L. Brossay, M. Degano, H. Iijima, M. Gui, I. A. Wilson, and M. Kronenberg Structural requirements for antigen presentation by mouse CD1 PNAS, August 29, 2000; 97(18): 10156 - 10161. [Abstract] [Full Text] [PDF]
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M. Skold, N. N. Faizunnessa, C.-R. Wang, and S. Cardell CD1d-Specific NK1.1+ T Cells with a Transgenic Variant TCR J. Immunol., July 1, 2000; 165(1): 168 - 174. [Abstract] [Full Text] [PDF]
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D. Zeng, M.-K. Lee, J. Tung, A. Brendolan, and S. Strober Cutting Edge: A Role for CD1 in the Pathogenesis of Lupus in NZB/NZW Mice J. Immunol., May 15, 2000; 164(10): 5000 - 5004. [Abstract] [Full Text] [PDF]
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D. Zeng, G. Gazit, S. Dejbakhsh-Jones, S. P. Balk, S. Snapper, M. Taniguchi, and S. Strober Heterogeneity of NK1.1+ T Cells in the Bone Marrow: Divergence from the Thymus J. Immunol., November 15, 1999; 163(10): 5338 - 5345. [Abstract] [Full Text] [PDF]
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S. Hong and L. Van Kaer Immune Privilege: Keeping an Eye on Natural Killer T Cells J. Exp. Med., November 1, 1999; 190(9): 1197 - 1200. [Full Text] [PDF]
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O. V. Naidenko, J. K. Maher, W. A. Ernst, T. Sakai, R. L. Modlin, and M. Kronenberg Binding and Antigen Presentation of Ceramide-containing Glycolipids by Soluble Mouse and Human CD1d Molecules J. Exp. Med., October 18, 1999; 190(8): 1069 - 1080. [Abstract] [Full Text] [PDF]
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G. Szalay, C. H. Ladel, C. Blum, L. Brossay, M. Kronenberg, and S. H. E. Kaufmann Cutting Edge: Anti-CD1 Monoclonal Antibody Treatment Reverses the Production Patterns of TGF-{beta}2 and Th1 Cytokines and Ameliorates Listeriosis in Mice J. Immunol., June 15, 1999; 162(12): 6955 - 6958. [Abstract] [Full Text] [PDF]
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G. Eberl, R. Lees, S. T. Smiley, M. Taniguchi, M. J. Grusby, and H. R. MacDonald Tissue-Specific Segregation of CD1d-Dependent and CD1d-Independent NK T Cells J. Immunol., June 1, 1999; 162(11): 6410 - 6419. [Abstract] [Full Text] [PDF]
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Y.-H. Chen, B. Wang, T. Chun, L. Zhao, S. Cardell, S. M. Behar, M. B. Brenner, and C.-R. Wang Expression of CD1d2 on Thymocytes Is Not Sufficient for the Development of NK T Cells in CD1d1-Deficient Mice J. Immunol., April 15, 1999; 162(8): 4560 - 4566. [Abstract] [Full Text] [PDF]
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L. Schofield, M. J. McConville, D. Hansen, A. S. Campbell, B. Fraser-Reid, M. J. Grusby, and S. D. Tachado CD1d-Restricted Immunoglobulin G Formation to GPI-Anchored Antigens Mediated by NKT Cells Science, January 8, 1999; 283(5399): 225 - 229. [Abstract] [Full Text]
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Y.-H. Chiu, J. Jayawardena, A. Weiss, D. Lee, S.-H. Park, A. Dautry-Varsat, and A. Bendelac Distinct Subsets of CD1d-restricted T Cells Recognize Self-antigens Loaded in Different Cellular Compartments J. Exp. Med., January 4, 1999; 189(1): 103 - 110. [Abstract] [Full Text] [PDF]
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S. Tangri, L. Brossay, N. Burdin, D. J. Lee, M. Corr, and M. Kronenberg Presentation of peptide antigens by mouse CD1 requires endosomal localization and protein antigen processing PNAS, November 24, 1998; 95(24): 14314 - 14319. [Abstract] [Full Text] [PDF]
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L. Brossay, O. Naidenko, N. Burdin, J. Matsuda, T. Sakai, and M. Kronenberg Cutting Edge: Structural Requirements for Galactosylceramide Recognition by CD1-Restricted NK T Cells J. Immunol., November 15, 1998; 161(10): 5124 - 5128. [Abstract] [Full Text] [PDF]
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L. Brossay, M. Chioda, N. Burdin, Y. Koezuka, G. Casorati, P. Dellabona, and M. Kronenberg CD1d-mediated Recognition of an alpha -Galactosylceramide by Natural Killer T Cells Is Highly Conserved through Mammalian Evolution J. Exp. Med., October 19, 1998; 188(8): 1521 - 1528. [Abstract] [Full Text] [PDF]
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N. Burdin, L. Brossay, Y. Koezuka, S. T. Smiley, M. J. Grusby, M. Gui, M. Taniguchi, K. Hayakawa, and M. Kronenberg Selective Ability of Mouse CD1 to Present Glycolipids: {alpha}-Galactosylceramide Specifically Stimulates V{alpha}14+ NK T Lymphocytes J. Immunol., October 1, 1998; 161(7): 3271 - 3281. [Abstract] [Full Text] [PDF]
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J. L. Matsuda, L. Gapin, N. Fazilleau, K. Warren, O. V. Naidenko, and M. Kronenberg Natural killer T cells reactive to a single glycolipid exhibit a highly diverse T cell receptor beta repertoire and small clone size PNAS, October 23, 2001; 98(22): 12636 - 12641. [Abstract] [Full Text] [PDF]
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