期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 198, 期 1, 页码 173-181出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20030446
关键词
NKT cell; alpha-galactosylceramide; CD1d; tetramer; melanoma
资金
- NCI NIH HHS [K24 CA81293, K24 CA081293, R01 CA2511] Funding Source: Medline
GD3, a ganglioside expressed on human melanoma, can be recognized by the humoral immune system. In this paper, we demonstrate that immunizing mice with the human melanoma cell line SK-MEL-28 (GD3(+) GM2(-) CD1(-)) or with syngeneic APCs loaded with GD3 can induce a GD3-reactive natural killer T (NKT) cell response. GD3-reactive NKT cells were detected among splenocytes of immunized mice at frequencies of similar to1:2,000 both by ELISPOT and GD3-loaded mouse CD1d tetramer analysis. GD3-reactive NKT cells did not react with GM2, a closely related ganglioside, and were not detectable in unimmunized mice. GD3-reactive NKT cells initially produced IL-4 and IFN-gamma followed by IL-10. They were CD1d restricted in that reactivity was abrogated when APCs were blocked with anti-CD1d monoclonal antibody before being loaded with GD3 or when APCs from CD1d knockout mice were used. Because SK-MEL-28 does not express any isoform of human CD1, GD3 must be cross-presented by murine APCs in vivo. This is the first analysis of a natural ligand for mouse NKT cells and the first definitive paper of cross-presentation to NKT cells. This could be a mechanism for NKT cell recognition of tumor gangliosides in CD1(-) tumors.
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