Lipid antigen presentation in the immune system; lessons learned from CD 1 d knockout mice

Authors

  • Seokmann Hong,

    1. Howard Hughes Medical Institute, Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
    Search for more papers by this author
  • David C. Scherer,

    1. Howard Hughes Medical Institute, Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
    Search for more papers by this author
  • Nagendra Singh,

    1. Howard Hughes Medical Institute, Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
    Search for more papers by this author
  • Sanjeev K. Mendiratta,

    1. Pharmaceutical Research Laboratory, Kirin Brewery Co, Ltd., Takasaki-shi, Gunma, Japan.
    Search for more papers by this author
  • Isao Serizawa,

    1. Pharmaceutical Research Laboratory, Kirin Brewery Co, Ltd., Takasaki-shi, Gunma, Japan.
    Search for more papers by this author
  • Yasuhiko Koezuka,

    1. Pharmaceutical Research Laboratory, Kirin Brewery Co, Ltd., Takasaki-shi, Gunma, Japan.
    Search for more papers by this author
  • Luc Van Kaer

    Corresponding author
    1. Howard Hughes Medical Institute, Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
      Luc Van Kaer, Howard Hughes Medical Institute Department of Microbiology and Immunology Vanderbilt University School of Medicine 811 Light Hall Nashville TN 37232 USA Fax: 1615 343 2972 e-mail: vankael@ctrvax.vanderbilt.edu
    Search for more papers by this author

  • Acknowledgements
    This research was supported by the Howard Hughes Medical Institute. The authors would like to thank Drs W D. Martin. A, Boesteanu and S, Joyce for their contributions to the generation and initial characterization of CD Id knockout mice, and Drs S, Joyce and A. Bendelac for cell lines.

Luc Van Kaer, Howard Hughes Medical Institute Department of Microbiology and Immunology Vanderbilt University School of Medicine 811 Light Hall Nashville TN 37232 USA Fax: 1615 343 2972 e-mail: vankael@ctrvax.vanderbilt.edu

Abstract

Summary: CD I molecules represent a distinct lineage of antigen-presenting molecules chat are evolutionarily related to the classical major histocompatility complex (MHC) dass I and class II molecules, Unlike the classical MHC products that bind peptides, GDI molecules have evolved Co bind lipids and glycolipids, Murine and human CD Id molecules can present glycolipid antigens such as α-galactosylceramide (α-GalCer) to CD 1d-restricced natural killer (NK) T cells. Using CD 1d knockout mice we demonstrated chat CDI d expression is required for the development of NK T cells. These animals were also deficient in the rapid production of inter-leukin-4 and intcrferon-γ in response to stimulation by anti-CD3 antibodies. Despite these defects, CD Id knockout animals were able to generate strong T-helper type 1 (TH1) and TH2 responses. Spleen cells from these animals neither proliferated nor produced cytokines in response to stimulation by α-GalCer, Repeated injection of α-GalCer into wild-type but not CD 1 d mutant mice was able to clear metastatic tumors. We further showed that α-GalCer can inhibit disease in diabetes-prone non-obese diabetic mice. Collectively, these findings with CD ld knockout animals indicate a critical role for CD 1 d-dependent T cells in various disease conditions, and suggest that α-GalCer may be useful for therapeutic intervention in these diseases.

Ancillary