Microenvironmental stresses induce HLA‐E/Qa‐1 surface expression and thereby reduce CD8+ T‐cell recognition of stressed cells |
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| Authors: | Takanori Sasaki Takayuki Kanaseki Yosuke Shionoya Serina Tokita Sho Miyamoto Eri Saka Vitaly Kochin Akira Takasawa Yoshihiko Hirohashi Yasuaki Tamura Akihiro Miyazaki Toshihiko Torigoe Hiroyoshi Hiratsuka Noriyuki Sato |
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| Institution: | 1. Department of Pathology, Sapporo Medical University, Sapporo, Japan;2. Department of Oral Surgery, Sapporo Medical University, Sapporo, Japan;3. Department of Respiratory Medicine and Allergology, Sapporo Medical University, Sapporo, Japan;4. Department of Molecular Therapeutics, Center for Food and Medical Innovation, Hokkaido University, Sapporo, Japan |
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| Abstract: | Hypoxia and glucose deprivation are often observed in the microenvironment surrounding solid tumors in vivo. However, how they interfere with MHC class I antigen processing and CD8+ T‐cell responses remains unclear. In this study, we analyzed the production of antigenic peptides presented by classical MHC class I in mice, and showed that it is quantitatively decreased in the cells exposed to either hypoxia or glucose deprivation. In addition, we unexpectedly found increased surface expression of HLA‐E in human and Qa‐1 in mouse tumor cells exposed to combined oxygen and glucose deprivation. The induced Qa‐1 on the stressed tumor model interacted with an inhibitory NKG2/CD94 receptor on activated CD8+ T cells and attenuated their specific response to the antigen. Our results thus suggest that microenvironmental stresses modulate not only classical but also nonclassical MHC class I presentation, and confer the stressed cells the capability to escape from the CD8+ T‐cell recognition. |
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| Keywords: | Antigen presentation Glucose deprivation hypoxia HLA‐E MHC class I Microenvironmental stress Qa‐1 |
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