Published in Cancer Detection and Prevention 1997; 21(1):12-21.

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

I Huvent, C Cousin, A Kiss, PhD, C Bernard, JC D'Halluin, PhD

INSERM U124, Lille Institute of Cancer Research, Lille France

Address all correspondence and reprint requests to: Jean Claude D'Halluin, PhD, INSERM U124, Institut de Recherche sur le Cancer, 1 place de Verdun, 59045 Lille Cedex, France

ABSTRACT: All adenoviruses transform rodent cells in vitro, but only cells transformed by serotypes belonging to subgroups A (Adl2) 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/Adl2 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 Ad 12. Susceptibility of these transformed cell lines to NK cells was determined by cytolytic assays. The results obtained suggest that two of Adl2 E1A domains are required to induce resistance of the cell lines to NK cells.

KEY WORDS: adenovirus, serotypes, major histocompatibility complex class I, transformation, natural killer cells.