GD2 oligosaccharide: target for cytotoxic T lymphocytes.
Carbohydrate antigens rarely provide target epitopes for cytotoxic T lymphocytes (CTL). Disialoganglioside GD2 is a glycolipid expressed at high levels in human tumors and a small group of murine lymphomas (EL4, RBL5, RMA, RMA-S, A13, and BALBRVE). Immunization of C57B1/6 mice with irradiated EL4 cells stimulated a specific CTL response and protected these animals from engraftment of EL4 lymphoma. The CTL activity resided in the CD4-CD8+ population, was dependent on T cell receptor alpha/beta, and was not removed by anti-natural killer cell immunoabsorption, but was restricted to GD2 and H-2b bearing targets. CTL activity could be completely inhibited by GD2-oligosaccharide-specific monoclonal antibodies and their F(ab')2 fragments, but not by immunoglobulin G3 myelomas or antibodies against GD3 or GM2. Soluble GD2 did not inhibit specific tumor lysis. RMA-S lymphoma cells (GD2+H-2b-TAP2 deficient) were resistant to GD2-specific CTL. Sialic acid-containing peptides eluted from EL4 lymphoma cells could (a) stabilize H-2 molecules on RMA-S cells and (b) sensitize them for GD2-specific CTL. Control peptides (derived from vesicular stomatitis virus nucleoprotein peptide and GD2-negative lymphomas) could also stabilize H-2 on RMA-S, but were resistant to GD2-specific CTL. These H-2-binding peptides could be purified by anti-GD2 affinity chromatography. We postulate a new class of naturally occurring epitopes for T cells where branched-chain oligosaccharides are linked to peptides with anchoring motifs for the major histocompatibility complex class I pocket. While analogous to the haptens trinitrophenyl and O-beta-linked acetyl-glucosamine, the potential implications of natural carbohydrates as antigenic epitopes for CTL in biology are considerable.
Zhao
X J
XJ
Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York 10021, USA.
Cheung
N K
NK
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005732:Gangliosides / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology; D007114:Immunization; D015471:Leukemia, Basophilic, Acute / Q000276:immunology / Q000473:pathology; D008223:Lymphoma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009474:Neurons / Q000276:immunology; D051381:Rats; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000939:Epitopes; D005732:Gangliosides; D006183:H-2 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; C019403:ganglioside, GD2