Microenvironmental stresses induce HLA-E/Qa-1 surface expression and thereby reduce CD8(+) T-cell recognition of stressed cells.

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.

journal_name

Eur J Immunol

authors

Sasaki T,Kanaseki T,Shionoya Y,Tokita S,Miyamoto S,Saka E,Kochin V,Takasawa A,Hirohashi Y,Tamura Y,Miyazaki A,Torigoe T,Hiratsuka H,Sato N

doi

10.1002/eji.201545835

subject

Has Abstract

pub_date

2016-04-01 00:00:00

pages

929-40

issue

4

eissn

0014-2980

issn

1521-4141

journal_volume

46

pub_type

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