Cross-presentation of disialoganglioside GD3 to natural killer T cells Journal Article
| Authors: | Wu, D. Y.; Segal, N. H.; Sidobre, S.; Kronenberg, M.; Chapman, P. B. |
| Article Title: | Cross-presentation of disialoganglioside GD3 to natural killer T cells |
| Abstract: | 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 ∼1:2,000 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-γ 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. |
| Keywords: | controlled study; human cell; nonhuman; antigen expression; animal cell; mouse; animals; mice; melanoma; interleukin 10; interleukin 4; mice, inbred c57bl; antigen presentation; cytokines; amino acid sequence; molecular sequence data; gamma interferon; antigen recognition; melanoma cell; natural killer cell; killer cells, natural; cytokine production; antigen presenting cell; antigen-presenting cells; ganglioside gd3; ganglioside gm2; tetramer; cd1d antigen; immunization; gangliosides; antigens, cd1; galactosylceramides; interferon production; cd1d; nkt cell; α-galactosylceramide; humans; human; female; priority journal; article |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 198 |
| Issue: | 1 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2003-07-07 |
| Start Page: | 173 |
| End Page: | 181 |
| Language: | English |
| DOI: | 10.1084/jem.20030446 |
| PUBMED: | 12847141 |
| PROVIDER: | scopus |
| PMCID: | PMC2196074 |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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