SELECTIVE LOSS OF H-2D(S) ANTIGEN ON A MURINE-B LYMPHOMA DUE TO A POSTTRANSCRIPTIONAL BLOCK IN EXPRESSION

The major histocompatibility (MHC) class I antigens are coordinately e xpressed in most cells. However, some tumors or virus-infected cells l ack expression of one MHC class I antigen, while expression of the oth er MHC class I antigens is unaffected. We previously described the sel ective expression of MHC class I antigens on a B-cell lymphoma from SJ L/J mice called RCS5. This tumor expresses H-2K(s), but has lost cell surface expression of H-2D(s). To understand the mechanism responsible for the selective loss of H-2D(s) on the cell surface, we analysed H- 2D(s) mRNA and protein in the RCS5 tumor. Here we report that H-2D(s) mRNA was expressed in RCSS, but H-2D(s) protein was not detected in ce ll lysates. To determine whether the H-2D(s) mRNA from RCSS was able t o direct the synthesis of H-2D(s) protein, we performed cDNA cloning, in vitro translation and gene transfer experiments using a cell line r elated to RCSS (cRCS-X). Our results indicated that the inhibition of H-2D(s) expression in cRCS-X occurred after transcription of a non-def ective H-2D(s) mRNA. Furthermore, H-2DI antigen expression was restore d in cRCS-X using a retroviral vector to express the recombinant H-2D( s) cDNA. These results indicate that the inhibition of H-2D(s) express ion could be overcome either by out competing an inhibitor that functi ons in trans or by removing cis-acting regulatory sequences from the e ndogenous H-2D(s) mRNA.