The purpose of this research is to examine the role of recombinant retroviruses in murine leukemia. We will focus specifically on the consequences of expression of an altered envelope glycoprotein (gp70) in leukemic transformation. Using antibody probes directed to chemically synthesized peptides derived from the nucleotide sequence of a Moloney virus-derived recombinant virus, we have detected specific expression of a 70,000 dalton glycoprotein on normal peanut agglutinin positive thymus cells. This gp70, termed 81-TAg, is not expressed by bone marrow or splenic T-cells and thus defines a discrete differentiation antigen related to a leukemogenic recombinant virus. By using immunological markers, we will define the 81-TAg positive cell population as precisely as possible and try to determine if a correlation exists between this cell population and the target cells for leukemic transformation by recombinant viruses. We will also further characterize 81-TAg related molecules found in brain and testes to determine their relationship to the thymic molecule. Other probes will be prepared to further dissect the repertoire of polymorphic gp70s found in normal mouse tissues. These include monoclonal antibodies to endogenous gp70-related molecules as well as additional anti-synthetic peptide antibodies directed to specific amino acid sequences. We will use these reagents to analyze the distribution of gp70-related molecules and track progression of exogenous viral infection by methods including Western blotting, immune precipitation, fluorescence activated cell sorting, centrifugal elutriation, and tissue staining. These studies will provide valuable information regarding the role of recombinant retroviruses in murine leukemia as well as to define possible roles for gp70-related molecules in normal murine development.
