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NKT Ligand Conjugated Immunotherapy

  • Yasuyuki Ishii
Part of the Allergy Frontiers book series (ALLERGY, volume 6)

Abstract

Vα14-NKT cells express an invariant TCR α-chain and restricted TCR β-chains using Vβ8, Vβ7, and Vβ2 and are restricted by CD1d molecule, which can present glycolipids such as α-galactosylceramide (α-GalCer) groups. The representative compound among α-GalCer ligands is KRN7000, which was chemically modified from natural agelasphins of marine sponge. KRN7000 had been originally screened by the using in vivo assays for anti-tumor effects, and was subsequently qualified as a ligand for Vα14-NKT cells. When Vα14-NKT cells are activated by α-GalCer-pulsed professional antigen-presenting cells, e.g. dendritic cells (DCs), they produce various cytokines such as IL-2, IL-4, IL-10, IL-13, IL-17, IL-21 and IFN-γ, which are involved in the immune regulation between innate and acquired immunity. And, IL-12 production from the α-GalCer-pulsed DC after the interaction with Vα14-NKT cells is beneficial to the attenuation of tumor progression and of Th2-dominant allergic diseases. In addition, a novel delivery of α-GalCer lipsomes to splenic B220+ cells makes it possible to induce regulatory cells in vivo, and to suppress the secondary antibody responses in mice. Accumulated results suggest that a wide variety of NKT ligand-conjugated immunotherapies can be accomplished by the precise delivery of α-GalCer to the target cells expressing CD1d.

Keywords

Treg Cell Allergy Clin Immunol BDF1 Mouse CD1d Molecule IgG2a Antibody Response 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer 2010

Authors and Affiliations

  1. 1.Laboratory for Vaccine DesignRIKEN Research Center for Allergy and ImmunologyYokohamaJapan

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