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- W1517459791 abstract "Abstract Tumor antigens are mainly low-avidity antigens to T cells and unable to elicit effective anti-tumor immunity. Little knowledge on how low-avidity antigens elicit T cell response in vivo further hinders designing strategies to improve anti-tumor immune response. Using a unique mouse tumor model, we found that neither native tumor antigen nor majority of altered peptide ligands (APLs) derived from tumor antigen but only intermediate avidity APL was able to elicit robust cross-reactive tumor-specific CD8 T cell response. Central tolerance shifted T cell repertoire to allow host T cells only respond to low avidity APLs and spare the lower cross-reactivity to self antigens (tumor antigens). In addition, the functional avidity of cross-reactive tumor-specific CD8 T cells was over 1000 times less than that of pathogen-type antigen-specific CD8 T cells. These results indicate that the extremely low functional avidity and low cross-reactivity to native tumor antigen are two key reasons why APLs are ineffective for eliciting cytotoxic activity of CD8 T cells to kill tumor cells. Our further studies revealed that two distinct mechanisms control the functionality and responsiveness of tumor-specific CD8 T cells. This study also discovered a novel immunization strategy to enhance the functionality and responsiveness of tumor-specific CD8 T cells. Altogether, our study will shed light on strategies to enhance the efficacy of both immunotherapy and vaccination against cancers." @default.
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- W1517459791 date "2014-05-01" @default.
- W1517459791 modified "2023-10-17" @default.
- W1517459791 title "The change of T cell repertoire due to central tolerance determines the antigenic requirement and strategy for inducing effective anti-tumor CD8 T cell response (TUM2P.888)" @default.
- W1517459791 doi "https://doi.org/10.4049/jimmunol.192.supp.71.12" @default.
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