β5t shapes CD8 T cells without negative selection
| Autor: | Alison Jacques, Margaret C. Cam, Naozumi Ishimaru, Michael C. Kelly, Kensuke Takada, Da Yin, Melina Frantzeskakis, Izumi Ohigashi, Parirokh Awasthi, Sayumi Fujimori, Yousuke Takahama, Aya Ushio, Fusano Yamashita |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Proteasome Endopeptidase Complex Receptors Antigen T-Cell alpha-beta Thymic medulla T cell Immunology Apoptosis Thymus Gland CD8-Positive T-Lymphocytes Biology Epithelium Article Mice 03 medical and health sciences Negative selection 0302 clinical medicine medicine Animals Immunology and Allergy Cytotoxic T cell Cells Cultured Mice Knockout Thymocytes Base Sequence Sequence Analysis RNA High-Throughput Nucleotide Sequencing Cell Differentiation Epithelial Cells Dendritic Cells Tcr repertoire Cell biology Cortex (botany) Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure VDJ Exons CD8 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | The thymoproteasome expressed in thymic cortical epithelium optimizes the generation of CD8+ T cells. This study reveals that the thymoproteasome hardwires the TCR repertoire of CD8+ T cells with cortical positive selection independent of thymic negative selection processes. The thymoproteasome expressed specifically in thymic cortical epithelium optimizes the generation of CD8+ T cells; however, how the thymoproteasome contributes to CD8+ T cell development is unclear. Here, we show that the thymoproteasome shapes the TCR repertoire directly in cortical thymocytes before migration to the thymic medulla. We further show that the thymoproteasome optimizes CD8+ T cell production independent of the thymic medulla; independent of additional antigen-presenting cells, including medullary thymic epithelial cells and dendritic cells; and independent of apoptosis-mediated negative selection. These results indicate that the thymoproteasome hardwires the TCR repertoire of CD8+ T cells with cortical positive selection independent of negative selection in the thymus. Graphical Abstract |
| Databáze: | OpenAIRE |
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