We propose to identify ways in which anti-viral CTL recognize or fail to recognize leukemia virus cell surface antigen in the murine system. In particular, we plan to study why normal cells from AKXL mice, which carry the Akv-1 murine leukemia provirus, are recognized by C57B1/6 anti-AKR/Gross virus CTL, whereas cells from other AKXL mice which carry the highly related Akv-4 provirus, are not recognized by such antiviral CTL's. Green and coworkers have used standard immunological techniques including CTL recognition and induction assays and antiviral monoclonal antibody recognition assays that clearly indicate the importance of the viral antigen gp70 in the CTL recognition process. To further study viral epitope expression for recognition by CTL, I propose here to clone and compare by restriction mapping the Akv-1 and Akv-4 proviral DNA loci. The cell surface viral antigens expressed by these proviruses and recognized by CTL will then be studied and compared by transfecting recombinant proviral subclones into fibroblast or lymphoblastoid cell lines. After culturing the transfected cells in G418 selective medium, viral antigen expression will be assayed for by cytofluorography using antiviral monoclonal antibodies and by CTL functional assays. By these means, we can better define the viral elements necessary for CTL recognition and induction and better understand the promotion of tumor establishment resulting from the failure of these processes.
| White, H D; Roeder, D A; Green, W R (1994) An immunodominant Kb-restricted peptide from the p15E transmembrane protein of endogenous ecotropic murine leukemia virus (MuLV) AKR623 that restores susceptibility of a tumor line to anti-AKR/Gross MuLV cytotoxic T lymphocytes. J Virol 68:897-904 |
| White, H D; Roeder, D A; Lam, T et al. (1994) Major and minor Kb-restricted epitopes encoded by the endogenous ecotropic murine leukemia virus AKR623 that are recognized by anti-AKR/Gross MuLV CTL. Viral Immunol 7:51-9 |
| White, H D; Green, W R; Gine, N R (1993) Molecular cloning of infectious ecotropic murine leukemia virus AK7 from an emv-14-positive AKXL-5 mouse and the resistance of AK7 to recognition by cytotoxic T lymphocytes. J Virol 67:5045-50 |
| White, H D; Robbins, M D; Green, W R (1990) Mechanism of escape of endogenous murine leukemia virus emv-14 from recognition by anti-AKR/Gross virus cytolytic T lymphocytes. J Virol 64:2608-19 |
