C-terminal domain of the adenovirus E1A oncogene product is required for induction of cytotoxic T lymphocytes and tumor-specific transplantation immunity

Adenovirus genes required for the elicitation of adenovirus group C-specific cytolytic T lymphocytes (CTLs) and for the induction of adenovirus-specific transplantation antigen (TSTA) were identified by immunization with a library of adenovirus mutants. The group C Ad-specific CTL response was elicited by immunization with wild-type adenovirus type 5 (Ad5) or with recombinant adenoviruses containing Ad5 E1 A gene. The specific CTL response was also elicited by Ad5 virus constructs which express only the 12 S or 13 S El A early mRNA, but not with viruses unable to express E1 A protein sequences normally encoded by the ElA early messages. The induction of transplantation immunity against tumorigenic Ad-transformed cells was studied next. The product encoded by either 13 S and 12 S EIA mRNA alone was sufficient for strong TSTA activity. A series of viruses with mutations within the first axon of the ElA message also induced strong TSTA, while Ad5 mutants with lesions within the second axon failed to induce syngraft immunity. These results provide strong evidence that amino acid sequence encoded by the second axon of the Ad5 El A message is required, either directly or indirectly, for the induction of both Ad-specific CTL and Ad TSTA.