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Multiple defects in antigen presentation and T cell development by mice expressing cytoplasmic tail–truncated CD1d

Nature Immunology volume 3, pages 55–60 (2002)Cite this article

Abstract

For members of the CD1 family of β2-microglobulin–associated lipid-presenting molecules, tyrosine-based motifs in the cytoplasmic tail and invariant chain (Ii) govern glycoprotein trafficking through endosomal compartments. Little is known about the intracellular pathways of CD1 trafficking and antigen presentation. However, in vitro studies with cells transfected with mutant CD1 that had a truncated cytoplasmic tail have suggested a role for these tyrosine motifs in some, but not all, antigenic systems. By introducing a deletion of the tyrosine motif into the germ line, and through homologous recombination in embryonic stem cells, we now describe knock-in mice with the CD1d cytoplasmic tail deleted. Despite adequate surface CD1d expression and the presence of Ii, these mutant mice showed multiple and selective abnormalities in intracellular trafficking, antigen presentation and T cell development, demonstrating the critical functions of the CD1d cytoplasmic tail motif in vivo.

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Figure 1: CD1-TD knock-in mouse.
Figure 2: Surface expression of CD1-TD.
Figure 3: Altered trafficking of CD1-TD.
Figure 4: Differential recognition of CD1-TD by representatives of Vα14 and non-Vα14 CD1d-autoreactive hybridomas.
Figure 5: Impaired presentation of αGalCer by CD1-TD cells.
Figure 6: Decreased thymic selection of Vα14 NKT cells in CD1-TD mice.

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Acknowledgements

We thank B. Jabri, G. Waters and M. Weigert for advice and discussions and J. Goodhouse for help with confocal microscopy. Supported by grants from the Korea Research Foundation (grant 2001-015-DS0063 to S.-H. P.), ACS and NIH (to A. B.) as well as the Cancer Research Institute (Y.-H. C.), the Leukemia and Lymphoma Society of America (K. B.) and the Human Frontier Science Program (C. F.).

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Author notes

  1. Ya-Hui Chiu and Se-Ho Park: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Biology, Princeton University, Princeton, 08544, NJ, USA

    Ya-Hui Chiu, Se-Ho Park, Kamel Benlagha, Claire Forestier, Jayanthi Jayawardena-Wolf & Albert Bendelac

  2. Graduate school of Biotechnology, Korea University, Seoul, 136-701, South Korea

    Se-Ho Park

  3. Department of Chemistry and Biochemistry Brigham Young University, Provo, UT, USA

    Paul B. Savage

  4. Department of Immunology, Scripps Research Institute, La Jolla, 92037, CA, USA

    Luc Teyton

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Correspondence to Se-Ho Park or Albert Bendelac.

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Chiu, YH., Park, SH., Benlagha, K. et al. Multiple defects in antigen presentation and T cell development by mice expressing cytoplasmic tail–truncated CD1d. Nat Immunol 3, 55–60 (2002). https://doi.org/10.1038/ni740

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