Lipid antigen presentation in the immune system: Lessons learned from CD1d knockout mice

Seokmann Hong, David C. Scherer, Nagendra Singh, Sanjeev K. Mendiratta, Isao Serizawa, Yasuhiko Koezuka, Luc Van Kaer

Research output: Contribution to journalReview article

104 Scopus citations

Abstract

CD1 molecules represent a distinct lineage of antigen-presenting molecules that are evolutionarily related to the classical major histo-compatibility complex (MHC) class I and class II molecules. Unlike the classical MHC products that bind peptides, CD1 molecules have evolved to bind lipids and glycolipids. Murine and human CD1d molecules can present glycolipid antigens such as α-galactosylceramide (α-GalCer) to CD1d-restricted natural killer (NK) T cells. Using CD1d knockout mice we demonstrated that CD1d expression is required for the development of NK T cells. These animals were also deficient in the rapid production of interleukin-4 and interferon-γ in response to stimulation by anti-CD3 antibodies. Despite these defects, CD1d knockout animals were able to generate strong T-helper type 1 (T(H)1) and T(H)2 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 CD1d 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 CD1d knockout animals indicate a critical role for CD1d-dependent T cells in various disease conditions, and suggest that α-GalCer may be useful for therapeutic intervention in these diseases.

Original languageEnglish (US)
Pages (from-to)31-44
Number of pages14
JournalImmunological Reviews
Volume169
DOIs
StatePublished - Jul 29 1999
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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