Tumor cells expressing major histocompatibility complex class II and B7 activation molecules stimulate potent tumor-specific immunity.
In previous studies we have shown that the highly malignant mouse SaI sarcoma can be converted into an immunogenic tumor that is immunologically rejected by the autologous host if the tumor cells are transfected with and express syngeneic major histocompatibility complex (MHC) class II genes. Tumor cells expressing class II heterodimers truncated for the cytoplasmic regions of the alpha and beta chains, however, are as malignant as wild-type class II- tumors. These studies have contributed to the hypothesis that T-cell activation requires two signals: the engagement of the MHC class II/peptide complex of the antigen-presenting cell (APC) by the T cell receptor for antigen of the responding T cell and the transmittal of a second, or costimulatory, signal by the APC to the responding T cell. In this report we show that induction of tumor-specific immunity is facilitated by delivery of a costimulatory signal provided by the B7 activation molecule. Mice challenged with SaI cells bearing truncated class II molecules and transfected with B7 cDNA are immune to the transfectants and are protected against a challenge of wild-type class II-B7- ascites or solid SaI tumor. The induced immunity requires CD4+ T cells and is specific for the immunizing sarcoma cells. These results highlight the critical role of the B7 costimulatory pathway in stimulating long-term, tumor-specific immunity that is effective against high doses of challenging wild-type tumor and suggest a strategy for enhancing tumor rejection.
Baskar
S
S
Department of Biological Sciences, University of Maryland, Baltimore 21228.
Nabavi
N
N
Glimcher
L H
LH
Ostrand-Rosenberg
S
S
D000818:Animals; D000918:Antibody Specificity; D017951:Antigen Presentation; D002455:Cell Division / Q000276:immunology; D003593:Cytoplasm / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D005802:Genes, MHC Class II; D007109:Immunity; D007114:Immunization; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009857:Oncogenes; D012513:Sarcoma, Experimental / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D009363:Neoplasm Proteins