Cis- and trans-repression of class I major histocompatibility gene expression in Abelson virus-transformed murine leukemia.
Numerous tumor cell lines of leukemic origin are known to modulate cell surface expression of major histocompatibility complex (MHC) class I antigens resulting in alterations in their immune detection and tumorigenicity. We have been studying the mechanisms responsible for attenuation of MHC class I gene expression in an H-2 heterozygous (H-2b x H-2d) Abelson-Murine leukemia virus (A-MuLV)-transformed leukemic cell line (designated R8). Here we report that treatment of the R8 cell line with the protein synthesis inhibitor cycloheximide (CHX) increased H-2Kb steady-state messenger RNA (mRNA) levels several fold. The induced H-2Kb mRNA transcripts were functional, as demonstrated by their ability to be translated into immunoprecipitable H-2Kb alloantigen. H-2Kb null variants derived from the R8 cell line were shown to be the product of both cis- and trans-acting mechanisms, insomuch as the treatment of R8-derived H-2Kb non-expressor lines with CHX re-established expression of H-2Kb mRNA to the same extent as transfection of the variant cell line with the wild-type H-2Kb gene. Such findings indicate that downregulation of MHC class I gene expression is constitutive for the R8 leukemic cell line, a phenomenon that may be related to the immature pre-B-cell phenotype of this A-MuLV transformant.
Zeff
R A
RA
Department of Pathology, University of Connecticut Health Center, Farmington 06032.
Zhao
Y F
YF
Tatake
R
R
Lachman
H
H
Borriello
F
F
Nathenson
S G
SG
D000011:Abelson murine leukemia virus / Q000235:genetics*; D000199:Actins / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology; D002472:Cell Transformation, Viral; D003513:Cycloheximide / Q000494:pharmacology; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D005805:Genes, MHC Class I; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006657:Histones / Q000235:genetics; D007700:Kinetics; D007942:Leukemia, Experimental / Q000235:genetics / Q000276:immunology*; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D009693:Nucleic Acid Hybridization; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D000199:Actins; D000949:Histocompatibility Antigens Class II; D006657:Histones; D012334:RNA, Neoplasm; D003513:Cycloheximide