Fine specificity of natural killer T cells against GD3 ganglioside and identification of GM3 as an inhibitory natural killer T-cell ligand Journal Article


Authors: Park, J. E.; Wu, D. Y.; Prendes, M.; Lu, S. X.; Ragupathi, G.; Schrantz, N.; Chapman, P. B.
Article Title: Fine specificity of natural killer T cells against GD3 ganglioside and identification of GM3 as an inhibitory natural killer T-cell ligand
Abstract: GD3, a ganglioside expressed on melanoma, is the only tumour-associated glycolipid described to date that can induce a CD1d-restricted natural killer T (NKT)-cell response. We analysed the fine specificity of GD3-reactive NKT cells and discovered that immunization with GD3 induced two populations of GD3-reactive NKT cells. One population was CD4+ CD8- and was specific for GD3; the other population was CD4- CD8- and cross-reacted with GM3 in a CD1d-restricted manner, but did not cross-react with GM2, GD2, or lactosylceramide. This indicated that the T-cell receptors reacting with GD3 recognize glucose-galactose linked to at least one N-acetyl-neuraminic acid but will not accommodate a terminal N-acetylgalactosamine. Immunization with GM2, GM3, GD2, or lactosylceramide did not induce an NKT-cell response. Coimmunization of GM3-loaded antigen-presenting cells (APCs) with GD3-loaded APCs suppressed the NKT-cell response to GD3 in a CD1d-restricted manner. This suppressive effect was specific for GM3 and was a local effect lasting 2-4 days. In vitro, GM3-loaded APCs also suppressed the interleukin-4 response, but not the interferon-γ response, of NKT cells to α-galactosylceramide. However, there was no effect on the T helper type 2 responses of conventional T cells. We found that this suppression was not mediated by soluble factors. We hypothesize that GM3 induces changes to the APC that lead to suppression of T helper type 2-like NKT-cell responses. © 2008 Blackwell Publishing Ltd.
Keywords: controlled study; nonhuman; mouse; animals; mice; animal tissue; cell function; interleukin 4; animal experiment; animal model; in vitro study; mice, inbred c57bl; cell specificity; t lymphocyte receptor; th2 cell; immune tolerance; gamma interferon; ganglioside gd2; ligands; killer cells, natural; glucose; t-lymphocyte subsets; ganglioside gm3; c57bl 6 mouse; epitopes, t-lymphocyte; antigen presenting cell; antigen-presenting cells; ganglioside gd3; ganglioside gm2; alpha galactosylceramide; natural killer t cell; immunization; lactosylceramide; gangliosides; ganglioside; interleukin-4; galactose; antigens, cd1; galactosylceramides; cd1d; α-galactosylceramide; gm3; n acetylgalactosamine; n acetylneuraminic acid; cross reactions; g(m3) ganglioside
Journal Title: Immunologiya
Volume: 123
Issue: 1
ISSN: 0206-4952
Publisher: Meditsina Publishers  
Date Published: 2008-01-01
Start Page: 145
End Page: 155
Language: English
DOI: 10.1111/j.1365-2567.2007.02760.x
PUBMED: 18154620
PROVIDER: scopus
PMCID: PMC2433273
DOI/URL:
Notes: --- - "Cited By (since 1996): 10" - "Export Date: 17 November 2011" - "CODEN: IMMUA" - "Source: Scopus"
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MSK Authors
  1. Yue Wu
    8 Wu
  2. Govindaswami Ragupathi
    138 Ragupathi
  3. Paul Chapman
    308 Chapman
  4. Jun-Eui Park
    5 Park
  5. Xing-Gu Lu
    5 Lu