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 cos timulatory molecules become effective cellular vaccines against wild-t ype tumor. The improved immunity is dependent on newly induced tumor-s pecific CD8(+) and/or CD4(+) T cells and presumably occurs because the B7 transfectants provide the requisite second signal for activation o f T cells in conjunction with tumor cell-presented MHC class I/tumor p eptide and/or MHC class II/tumor peptide complexes, respectively. Sinc e B7 expression is such a potent enhancer of tumor immunity, and yet s ome tumors are immunogenic in the absence of B7 transfection, we have used class I(+)class II-transfected tumors to investigate whether cost imulatory 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 ex pression, 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 e xpressed by the tumor cells via an in vivo induction process. Experime nts 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 clas s I(+)class II-transfected tumor, generation oi tumor immunity require s induction of tumor cell-encoded B7 molecules that are mediated by th e cytoplasmic region of the transfected class II heterodimer.