: Nat Biotechnol 2000 Dec;18(12):1269-1272 Related Articles, Books, LinkOut
Enhanced major histocompatibility complex class I-dependent presentation of antigens modified with cationic and fusogenic peptides.
Laus R, Graddis TJ, Hakim I, Vidovic D
Dendreon Corporation, Seattle, WA 98121.
[Record supplied by publisher]
Soluble extracellular protein antigens are notoriously poor stimulators of CD8+ cytotoxic T-lymphocyte (CTL) responses, largely because these antigens have inefficient access to an endogenous cytosolic pathway of the major histocompatibility complex (MHC) class I-dependent antigen presentation. Here, we present a strategy that facilitates antigen penetration into the cytosol of antigen-presenting cells (APC) by addition to the antigen of charge-modifying peptide sequences. As a result of this intervention, the charge modification enhances antigen uptake into APC by counteracting the repulsive cell surface charge, and then endosomal membranes are disrupted with a subsequent release of antigen into the cytosol. This technology significantly improves MHC class I-dependent antigen presentation to CTL, enabling a more efficient generation of specific CTL immunity in vivo. The strategy described here has potential for use in developing efficient vaccines for antigen-specific immunotherapy of human malignancies.
PMID: 11101805 |
