Cross-presentation of disialoganglioside GD3 to natural killer T cells.
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 approximately 1:2000 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.
Wu
Dianna Y
DY
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Segal
Neil H
NH
Sidobre
Stephane
S
Kronenberg
Mitchell
M
Chapman
Paul B
PB
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000502:physiology; D018949:Antigens, CD1 / Q000502:physiology; D055610:Antigens, CD1d; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D016207:Cytokines; D005699:Galactosylceramides; D005732:Gangliosides; C026226:ganglioside, GD3