Aberrant biosynthesis and transport of class I major histocompatibility complex molecules in cells transformed with highly oncogenic human adenoviruses.
The expression of class I major histocompatibility complex antigens on the surface of cells transformed by adenovirus 12 (Ad12) is generally very low. The absence of class I antigens correlates with the high oncogenicity of this virus. In primary embryonal fibroblasts from transgenic mice that express both endogenous H-2 genes and a miniature swine class I gene (PD1), Ad12-mediated transformation results in complete suppression of cell surface expression of class I antigens, but only 50% of the cell lines tested demonstrated decreased steady state levels of class I mRNA. The complete absence of cell surface class I antigens is accompanied by decreased levels of newly synthesized class I molecules. Those molecules that are immunoprecipitated by class I-specific antibodies are assembled with beta 2-microglobulin, but their transport through the Golgi is inefficient. The biosynthesis of both the endogenous H-2K, H-2D, and the transgene product, PD1, is similarly altered in the transformed cells. The results suggest that Ad12 transformation is associated with both reduced synthesis rate and inefficient transport of class I molecules to the cell surface. This might be a general mechanism by which virus-infected or -transformed cells escape immune surveillance.
Shemesh
J
J
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
Ehrlich
R
R
D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D001692:Biological Transport; D002472:Cell Transformation, Viral; D005347:Fibroblasts / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature
D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger