Selective loss of H-2Ds antigen on a murine B lymphoma due to a post-transcriptional block in expression.
The major histocompatibility (MHC) class I antigens are coordinately expressed in most cells. However, some tumors or virus-infected cells lack expression of one MHC class I antigen, while expression of the other MHC class I antigens is unaffected. We previously described the selective expression of MHC class I antigens on a B-cell lymphoma from SJL/J mice called RCS5. This tumor expresses H-2Ks, but has lost cell surface expression of H-2Ds. To understand the mechanism responsible for the selective loss of H-2Ds on the cell surface, we analysed H-2Ds mRNA and protein in the RCS5 tumor. Here we report that H-2Ds mRNA was expressed in RCS5, but H-2Ds protein was not detected in cell lysates. To determine whether the H-2Ds mRNA from RCS5 was able to direct the synthesis of H-2Ds protein, we performed cDNA cloning, in vitro translation and gene transfer experiments using a cell line related to RCS5 (cRCS-X). Our results indicated that the inhibition of H-2Ds expression in cRCS-X occurred after transcription of a non-defective H-2Ds mRNA. Furthermore, H-2Ds antigen expression was restored in cRCS-X using a retroviral vector to express the recombinant H-2Ds cDNA. These results indicate that the inhibition of H-2Ds expression could be overcome either by out competing an inhibitor that functions in trans or by removing cis-acting regulatory sequences from the endogenous H-2Ds mRNA.
Department of Immunology and Microbiology, Wayne State University, Detroit, MI 48201, USA.
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H
Luo
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Sopchak
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SP
Lerman
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SR
King
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002458:Cell Fractionation; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D018014:Gene Transfer Techniques; D005805:Genes, MHC Class I / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D012323:RNA Processing, Post-Transcriptional / Q000276:immunology*; D014407:Tumor Cells, Cultured
D006183:H-2 Antigens