Abstract
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.
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We would like to thank Dr. David Urdal for critically reviewing the manuscript.
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Laus, R., Graddis, T., Hakim, I. et al. Enhanced major histocompatibility complex class I-dependent presentation of antigens modified with cationic and fusogenic peptides. Nat Biotechnol 18, 1269–1272 (2000). https://doi.org/10.1038/82377
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DOI: https://doi.org/10.1038/82377
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