1. A mechanistic study of immune system activation by fusion of antigens with the ligand-binding domain of CTLA4.
- Author
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Chinnasamy D, Tector M, Chinnasamy N, Dennert K, Kozinski KM, and Oaks MK
- Subjects
- Animals, Antibody Formation, Antigens genetics, Antigens, CD chemistry, Antigens, Differentiation chemistry, B7-1 Antigen immunology, B7-2 Antigen immunology, CTLA-4 Antigen, Dendritic Cells drug effects, Humans, Immunoglobulin G immunology, Ligands, Mice, Protein Structure, Tertiary, Recombinant Fusion Proteins genetics, T-Lymphocytes immunology, T-Lymphocytes, Cytotoxic immunology, Antigens immunology, Antigens, CD genetics, Antigens, Differentiation genetics, Lymphocyte Activation, Recombinant Fusion Proteins immunology
- Abstract
Fusion proteins consisting of the ligand-binding domain of CTLA4 covalently attached to an antigen (Ag) are potent immunogens. This fusion strategy effectively induces Ag-specific immunity both when introduced as a DNA-based vaccine and as a recombinant protein. CTLA4 is a ligand for B7 molecules expressed on the surface of antigen-presenting cells (APCs), and this interaction is critical for the fusion protein to stimulate Ag-specific immunity. We show that interaction of the fusion protein with either B7-1 or B7-2 is sufficient to stimulate immune activity, and that T cells are essential for the development of IgG responses. In addition, we demonstrate that human dendritic cells (DCs) pulsed with CTLA4-Ag fusion proteins can efficiently present Ag to T cells and induce an Ag-specific immune response in vitro. These studies provide further mechanistic understanding of the process by which CTLA4-Ag fusion proteins stimulate the immune system, and represent an efficient means of generating Ag-specific T cells for immunotherapy.
- Published
- 2006
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