Cross-presentation of Disialoganglioside GD3 to Natural Killer T Cells
| Autor: | Stephane Sidobre, Neil H. Segal, Mitchell Kronenberg, Paul B. Chapman, Dianna Y. Wu |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Molecular Sequence Data
Immunology Antigen presentation CD1 Antigen-Presenting Cells Galactosylceramides chemical and pharmacologic phenomena CD1d Article Antigens CD1 Mice 03 medical and health sciences 0302 clinical medicine Immune system Antigen Gangliosides melanoma Animals Humans Immunology and Allergy Amino Acid Sequence Antigen-presenting cell 030304 developmental biology α-galactosylceramide Antigen Presentation 0303 health sciences biology tetramer Cross-presentation hemic and immune systems Natural killer T cell 3. Good health Killer Cells Natural Mice Inbred C57BL CD1D biology.protein Cytokines Female Immunization lipids (amino acids peptides and proteins) Antigens CD1d NKT cell 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|