Adenovirus type 5 E3 gene products interfere with the expression of the cytolytic T cell immunodominant E1a antigen.

Effects of mutations in the adenovirus 5 (Ad 5) E3 transcription unit on the immune Tc cell response to Ad 5 were investigated. We observed enhanced lysis of L929 target cells infected with the E3 defective mutant viruses dl 327 and dl 355 compared to wild-type (wt) Ad 5 by Ad 5 immune Tc cells. This enhanced lysability was not due to E3 effects on the cell surface expression of class I MHC H-2Kk molecules as determined by monoclonal antibody binding or alloreactive Tc cell recognition. Furthermore MHC class I molecules were able to efficiently present vaccinia virus antigens in the presence of the Ad 5 E3 genes, excluding functional modification of class I MHC antigens by E3 gene products. When levels of the Ad 5 immunodominant antigen E1a were compared between wt and E3 mutant viruses, we observed an 8- to 10-fold increase in E1a levels in E3 mutant-infected cells over wt Ad 5-infected cells. No differences were observed between these viruses at the mRNA level. We conclude that E3 products interfere with Ad 5 immune Tc cell responses by some post-transcriptional mechanism which reduces expression of the E1a immunodominant antigen.