G(D2) oligosaccharide: Target for cytotoxic T-lymphocyte (CTL) (Meeting abstract).

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

G(D2) oligosaccharide: Target for cytotoxic T-lymphocyte (CTL) (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 36:A2846 1995. Unique Identifier : AIDSLINE ICDB/96610619
Zhao X; Cheung NV; Dept. of Pediatrics, Memorial Sloan Kettering Cancer Center, New; York, NY 10021

Abstract: Carbohydrate antigens rarely provide target epitopes for CTL. Disialo-ganglioside G(D2) is expressed at high levels among human tumors (neuroblastomas, SCLC, melanomas, sarcomas, brain tumors) and a small group of murine lymphomas. Immunization of C57Bl/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- and CD8+ population, was dependent on TCR alpha beta and not removed by anti-NK immunoabsorption, but was restricted to GD2-oligosaccharide and H-2b bearing targets. CTL activity was completely inhibited by GD2-oligosaccharide specific monoclonal antibodies and their F(ab')2 fragments, but not by a large panel of IgG3 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 (1) stabilize H-2 molecules on RMA-S cells, and (2) sensitize them for GD2-specific CTL. Control peptides (derived from VSV-NP and G(D2)-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 epitopes for T cells where branched-chain carbohydrate residues are linked to peptides that bind to the MHC class I pocket. While analogous to the hapten TNP, the potential implications of carbohydrates as antigenic epitopes for CTLs in biology are considerable.

Keywords: Animal CD4-Positive T-Lymphocytes/IMMUNOLOGY CD8-Positive T-Lymphocytes/IMMUNOLOGY G(M2) Ganglioside/*IMMUNOLOGY Gangliosides/*IMMUNOLOGY *Immunotherapy, Adoptive Lymphoma/*IMMUNOLOGY/*THERAPY Mice Oligosaccharides/*IMMUNOLOGY T-Lymphocytes, Cytotoxic/*IMMUNOLOGY ABSTRACT
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M9640027

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