Rejection of MHC class II-transfected tumor cells requires induction of tumor-encoded B7-1 and/or B7-2 costimulatory molecules.
Many tumor cells that have been transfected with genes encoding B7 costimulatory molecules become effective cellular vaccines against wild-type tumor. The improved immunity is dependent on newly induced tumor-specific CD8+ and/or CD4+ T cells and presumably occurs because the B7 transfectants provide the requisite second signal for activation of T cells in conjunction with tumor cell-presented MHC class I/tumor peptide and/or MHC class II/tumor peptide complexes, respectively. Since B7 expression is such a potent enhancer of tumor immunity, and yet some tumors are immunogenic in the absence of B7 transfection, we have used class I+ class-II-transfected tumors to investigate whether costimulatory molecules are also involved in rejection of immunogenic, non-B7-transfected tumor. Blocking studies with B7 mAbs demonstrate that induction of tumor immunity in naive mice requires B7-1 and/or B7-2 expression, while experiments with tumor-primed mice indicate that once antitumor immunity is established, expression of B7 is not necessary. Flow cytometry analyses demonstrate that costimulatory molecules are expressed by the tumor cells via an in vivo induction process. Experiments with class II genes with truncated cytoplasmic tails indicate that the cytoplasmic region of the tumor-expressed class II heterodimer is involved in induction of B7. We therefore conclude that for this class I+ class II-transfected tumor, generation of tumor immunity requires induction of tumor cell-encoded B7 molecules that are mediated by the cytoplasmic region of the transfected class II heterodimer.
Baskar
S
S
Department of Biological Sciences, University of Maryland, Baltimore 21228 USA.
Clements
V K
VK
Glimcher
L H
LH
Nabavi
N
N
Ostrand-Rosenberg
S
S
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D018122:B7-1 Antigen / Q000096:biosynthesis*; D051940:B7-2 Antigen; D003593:Cytoplasm / Q000276:immunology; D005260:Female; D006084:Graft Rejection; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D007116:Immunization, Passive; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D008805:Mice, Inbred A; D009368:Neoplasm Transplantation; D012513:Sarcoma, Experimental / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D014162:Transfection / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins