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A mechanistic study of immune system activation by fusion of antigens with the ligand-binding domain of CTLA4.
- Source :
-
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2006 Dec; Vol. 55 (12), pp. 1504-14. Date of Electronic Publication: 2006 Apr 13. - Publication Year :
- 2006
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 0340-7004
- Volume :
- 55
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Cancer immunology, immunotherapy : CII
- Publication Type :
- Academic Journal
- Accession number :
- 16612600
- Full Text :
- https://doi.org/10.1007/s00262-006-0153-7