Generation of Adenovirus-Specific Cytotoxic T Lymphocytes

When using adenovirus as a vector for the delivery of transgenes, the induction of a cytotoxic T lymphocytes (CTL) can limit the longevity of the transgene expression (1 ,2 ). To detect the CTL response to adenovirus proteins or inserted transgenes in a mouse model, even with multiple in vivo immunizations, a secondary in vitro restimulation is necessary. The CTL response to adenovirus tends to focus on one or a few immunodominant epitopes. Using secondary in vitro restimulation of spleen cells from primed mice as described here, an adenovirus-specific, MHC class I-restricted CTL response has been generated that recognizes different immunodominant adenovirus antigens depending on the haplotype of the mice (3 ,4 ). Using various adenovirus deletion mutants or transfectants expressing individual adenovirus proteins, it is possible to map the CTL antigens. With this knowledge, it is possible to investigate methods for reducing or limiting the CTL response.