This research project is designed to identify and characterize the cell membrane receptor for murine leukemogenic retroviruses. Three related hypotheses will be tested: 1) that cell membrane receptors for leukemogenic retroviruses share serologically recognizable structures with the idiotypic determinants of anti-retroviral antibodies; 2) that anti-idiotypic antibodies against anti-retroviral antibodies can identify and isolate retroviral receptors; and 3) the retrovirus receptor is a leukemia specific marker. Two separate but related experimental approaches will test the above hypotheses. First, anti-idiotypic antibodies against anti-retroviral antibodies will be tested for their ability to bind to retrovirus-induce leukemias or to fibroblasts susceptible to infection by leukemogenic retroviruses. Those anti-idiotypic antibodies that demonstrate leukemia-specific binding to infectable fibroblasts, or both will be evaluated for their ability to compete with leukemogenic retroviruses for binding to cells expressing relevant receptors. Infection inhibition assays will similarly be performed to select for anti-idiotypic antibodies with anti-receptor activity. Those antibodies that fulfill the above criteria will serve to isolate and characterize the cell membrane structure to which they bind. The second approach involves production of monoclonal antibodies against: 1) cell membranes of retroviral-induced leukemias, and 2) fibroblasts susceptible to leukemogenic retrovirus infection. Antibodies thus generated will be screened for their ability to inhibit retrovirus infection and compete with virus for binding to receptor-bearing cells. Those antibodies demonstrating the above characteristics will be assayed for anti-(anti-gp70) idiotype binding and used to isolate the cell membrane structure to which they bind.
| Ardman, B; DiMambro, E; Levy, S B et al. (1987) Idiotype mimicry by a differentiation antigen on Friend erythroleukemia cells. J Immunol 139:2038-43 |
