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• W1830835774 abstract "Several strategies that increase proteasomal degradation of antigen have been shown to improve MHC class I presentation of antigen. Because recent studies have demonstrated that the centrosome is a subcellular compartment rich in proteasomes, we hypothesized that targeting a tumor antigen to centrosomal compartments would enhance both the MHC class I presentation of antigen and the vaccine potency. We, therefore, created a chimera of gamma-tubulin, an established centrosomal marker, with a model tumor antigen, human papillomavirus type 16 (HPV-16) E7, in a DNA vaccine. The linkage of gamma-tubulin to E7-targeted antigen to centrosomal compartments, resulted in enhanced MHC class I presentation of E7, and led to a marked increase in the number of E7-specific CD8(+) T-cell precursors as well as a potent CD4-independent antitumor effect against an E7-expressing tumor cell line, TC-1. In addition, vaccination with gamma-tubulin/E7 DNA in transporter associated with antigen presentation (TAP)-1-knockout mice revealed that the enhancement of E7-specific CD8(+) T-cell immune responses is TAP-1-dependent. Our data suggest that the centrosome may be an important locus for MHC class I antigen processing and that targeting antigen to the centrosome can improve DNA vaccine potency." @default.
• W1830835774 created "2016-06-24" @default.
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• W1830835774 date "2003-05-15" @default.
• W1830835774 modified "2023-10-18" @default.
• W1830835774 title "Enhancing major histocompatibility complex class I antigen presentation by targeting antigen to centrosomes." @default.
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• W1830835774 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12750257" @default.
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