期刊
IMMUNITY
卷 55, 期 6, 页码 982-+出版社
CELL PRESS
DOI: 10.1016/j.immuni.2022.04.016
关键词
-
类别
资金
- Immunology Training Grant at the University of Chicago [T32 AI007090]
- American Association of Immunologists
- [R01 CA16670]
- [P30 CA014599]
This study demonstrates the importance of MHC-I cross-dressing in regulating anti-tumor immunity. In addition to quantitatively enhancing tumor antigen presentation, it also enables dendritic cells to more accurately mirror the cancer cell peptidome.
Antigen cross-presentation, wherein dendritic cells (DCs) present exogenous antigen on major histocompatibility class I (MHC-I) molecules, is considered the primary mechanism by which DCs initiate tumor-specific CD8(+) T cell responses. Here, we demonstrate that MHC-I cross-dressing, an antigen presentation pathway in which DCs acquire and display intact tumor-derived peptide:MHC-I molecules, is also important in orchestrating anti-tumor immunity. Cancer cell MHC-I expression was required for optimal CD8(+) T cell activation in two subcutaneous tumor models. In vivo acquisition of tumor-derived peptide:MHC-I molecules by DCs was sufficient to induce antigen-specific CD8(+) T cell priming. Transfer of tumor-derived human leukocyte antigen (HLA) molecules to myeloid cells was detected in vitro and in human tumor xenografts. In conclusion, MHC-I cross-dressing is crucial for anti-tumor CD8(+) T cell priming by DCs. In addition to quantitatively enhancing tumor antigen presentation, MHC cross-dressing might also enable DCs to more faithfully and efficiently mirror the cancer cell peptidome.
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