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Hybrid antibody-mediated lysis of virus-infected cells
Authors:U D Staerz  J W Yewdell  M J Bevan
Abstract:Previously, cytotoxic T lymphocytes (CTL) had only been focused by hybrid antibodies to normal, cell-surface proteins and haptenated surface structures. In this report, we extend the application of this technology to mediate lysing of virus-infected cells by nonspecific CTL. Heteroconjugated antibodies between the anti-T cell antigen receptor antibody, F23.1, and monoclonal antibodies against either the hemagglutinin or nucleoprotein of the influenza virus PR/8 were constructed. We show in the present report that these bispecific constructs can target virus-infected cells for lysis according to the specificity of the virus-protein reactive monoclonal antibodies. Furthermore, even a virus protein that is only expressed in small quantities on the cell surface, such as nucleoprotein, can be exploited as target structure for heteroconjugated antibodies. These studies show that hybrid antibodies can focus a CTL response on virus-infected cells which might in the future be used to mount an immune response in situations without sufficient normal cellular defense.
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