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Microenvironmental stresses induce HLA‐E/Qa‐1 surface expression and thereby reduce CD8 + T‐cell recognition of stressed cells
Author(s) -
Sasaki Takanori,
Kanaseki Takayuki,
Shionoya Yosuke,
Tokita Serina,
Miyamoto Sho,
Saka Eri,
Kochin Vitaly,
Takasawa Akira,
Hirohashi Yoshihiko,
Tamura Yasuaki,
Miyazaki Akihiro,
Torigoe Toshihiko,
Hiratsuka Hiroyoshi,
Sato Noriyuki
Publication year - 2016
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201545835
Subject(s) - biology , cd8 , cytotoxic t cell , mhc class i , antigen , major histocompatibility complex , antigen presentation , t cell , microbiology and biotechnology , immunology , immune system , in vitro , biochemistry
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.