MHC class I heavy chain mRNA must exceed a threshold level for the reconstitution of cell surface expression of class I MHC complexes in cells transformed by the highly oncogenic adenovirus 12.
In primary embryonal fibroblasts from transgenic mice expressing H-2(b) genes and a miniature swine class I transgene (PD1), transformation with adenovirus 12 results in suppression of assembly and cell surface expression of all class I complexes. Cell surface expression of PD1 can be recovered by transfecting the cells with peptide transporter genes. However, reconstitution of the H-2Kb gene expression requires, in addition, a 2-fold increase in the steady state level of the H-2Kb mRNA that can be attained by treatment of the cells with interferons or by transfecting them with the H-2Kb gene. A detailed analyses of the biogenesis of class I molecules has revealed the steady state expression of free class I heavy chains that are not converted into conformed complexes even when peptide transporter genes are overexpressed. The fact that class I complex assembly seems to be highly inefficient in certain cell lines might be a major in vivo obstacle for the elimination of transformed or virus-infected cells by cytotoxic T lymphocytes, especially in view of the fact that the level of class I gene transcription is often down-regulated in cancer cells and/or that assembly of class I major histocompatibility complexes can be subverted by virus-encoded proteins.
Fromm
S V
SV
Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Mey-Tal
S W
SW
Coligan
J E
JE
Schechter
C
C
Ehrlich
R
R
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics; D005347:Fibroblasts; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics; D006183:H-2 Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D007372:Interferons / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D014162:Transfection / Q000235:genetics; D014170:Transformation, Genetic / Q000235:genetics
D004268:DNA-Binding Proteins; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D007976:Leupeptins; C075396:PD1 protein, pig; D010455:Peptides; D012333:RNA, Messenger; D007372:Interferons; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde