Downregulation of major histocompatibility complex class I expression and susceptibility to natural killer cells in cells transformed with the oncogenic adenovirus 12 are regulated by different E1A domains.
All adenoviruses transform rodent cells in vitro, but only cells transformed by serotypes belonging to subgroups A (Ad12) and B (Ad3) are tumorigenic for immunocompetent animals. In these cells, the expression of major histocompatibility complex (MHC) class I antigens is repressed and might allow them to escape from recognition by cytotoxic T lymphocytes and to develop in tumor. Furthermore, these cell lines appear resistant to lysis by natural killer (NK) cells. To determine the E1A domain(s) responsible for these properties several cell lines were created by transforming baby rat kidney cells with a set of plasmids expressing different Ad2/Ad12 hybrid E1A gene products. The class I gene expression was inhibited in cells expressing the Ad12 13S mRNA product and in cells transformed with Ad2/Ad12 hybrid E1A gene product harboring the C-terminal part of the conserved region (CR) 3 of Ad12. Susceptibility of these transformed cell lines to NK cells was determined by cytolytic assays. The results obtained suggest that two of Ad12 E1A domains are required to induce resistance of the cell lines to NK cells.
Huvent
I
I
INSERM U124, Institute of Cancer Research, Lille, France.
Cousin
C
C
Kiss
A
A
Baroni de Moraes
M T
MT
Bernard
C
C
D'Halluin
J C
JC
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D002472:Cell Transformation, Viral / Q000502:physiology*; D015536:Down-Regulation; D005091:Exons; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000276:immunology / Q000821:virology; D007694:Killer Cells, Natural / Q000276:immunology*; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D017500:Adenovirus E1A Proteins; D015395:Histocompatibility Antigens Class I