Cis- and trans-repression of class I major histocompatibility gene expression in Abelson virus-transformed murine leukemia

R. A. Zeff, Y. F. Zhao, R. Tatake, H. Lachman, F. Borriello, S. G. Nathenson

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5 Scopus citations

Abstract

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-2(d)) 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.

Original languageEnglish (US)
Pages (from-to)524-532
Number of pages9
JournalBlood
Volume78
Issue number2
Publication statusPublished - Jan 1 1991
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Zeff, R. A., Zhao, Y. F., Tatake, R., Lachman, H., Borriello, F., & Nathenson, S. G. (1991). Cis- and trans-repression of class I major histocompatibility gene expression in Abelson virus-transformed murine leukemia. Blood, 78(2), 524-532.