Microenvironmental stresses induce HLA-E/Qa-1 surface expression and thereby reduce CD8+ T-cell recognition of stressed cells
Microenvironmental stresses induce HLA-E/Qa-1 surface expression and thereby reduce CD8+ T-cell recognition of stressed cells
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DOI：
10.1002/eji.201545835
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发表时间：
2016-04-01
影响因子：
5.4
通讯作者：
Sato, Noriyuki
中科院分区：
文献类型：
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作者：
Sasaki, Takanori;Kanaseki, Takayuki;Sato, Noriyuki
缺氧和葡萄糖剥夺常在体内实体肿瘤周围的微环境中观察到。然而，它们如何干扰MHC I类抗原加工和CD 8（+）T细胞应答仍不清楚。在这项研究中，我们分析了小鼠中经典MHC I类呈递的抗原肽的产生，并表明在缺氧或葡萄糖剥夺的细胞中，抗原肽的产生量减少。此外，我们意外地发现暴露于氧和葡萄糖联合剥夺的人类HLA-E和小鼠肿瘤细胞中Qa-1的表面表达增加。在应激肿瘤模型上诱导的Qa-1与活化的CD 8（+）T细胞上的抑制性NKG 2/CD 94受体相互作用，并减弱其对抗原的特异性应答。因此，我们的研究结果表明，微环境压力不仅调节经典的，而且还非经典的MHC I类呈递，并赋予应激细胞逃避CD 8（+）T细胞识别的能力。
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.