Efficient activation of Vα14 invariant NKT cells by foreign lipid antigen is associated with concurrent dendritic cell-specific self recognition

Lu Cheng, Aito Ueno, Suzanne Cho, Jin S. Im, Susanne Golby, Sheng Hou, Steven A. Porcelli, Yang Yang

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

A burst release of cytokines by Vα14 invariant NKT (iNKT) cells upon their TCR engagement critically regulates innate and adaptive immune responses. However, it remains unclear in vivo why iNKT cells respond efficiently to microbial or intracellular lipid Ags that are at low levels or that possess suboptimal antigenicity. We found that dendritic cells (DCs) potentiated/NKT cells to respond to a minimal amount of ligand α-galactosylceramide (αGalCer) through CD1d-dependent autoreactivc responses that require endosomal processing and CD1d trafficking. The ability of potentiation of NKT cells was DC specific and did not depend on costimulatory signals and IL-12 production by DCs. However, DCs that failed to synthesize a major endogenous lipid Ag isoglobotrihexosylceramide were unable to potentiate NKT cells for efficient activation. Further analysis showed that differences in the level and pattern of endogenous lipid Ag presentation differentiate DCs and B cells for effective potentiation and subsequent activation of iNKT cells in the presence of an exogenous Ag. Thus, CD1d-dependent potentiation by DCs may be crucial for iNKT cell-mediated immunity against infectious agents.

Original languageEnglish (US)
Pages (from-to)2755-2762
Number of pages8
JournalJournal of Immunology
Volume178
Issue number5
StatePublished - Mar 1 2007

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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