title: 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.
authors.affiliation: Department of Pathology, Sapporo Medical University, Sapporo, Japan.|Department of Oral Surgery, Sapporo Medical University, Sapporo, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Department of Pathology, Sapporo Medical University, Sapporo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kanaseki
authors.affiliation: Department of Pathology, Sapporo Medical University, Sapporo, Japan.|Department of Respiratory Medicine and Allergology, Sapporo Medical University, Sapporo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Shionoya
authors.affiliation: Department of Pathology, Sapporo Medical University, Sapporo, Japan.
authors.forename: Serina
authors.initials: S
authors.lastname: Tokita
authors.affiliation: Department of Pathology, Sapporo Medical University, Sapporo, Japan.|Department of Oral Surgery, Sapporo Medical University, Sapporo, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Miyamoto
authors.affiliation: Department of Pathology, Sapporo Medical University, Sapporo, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Saka
authors.affiliation: Department of Pathology, Sapporo Medical University, Sapporo, Japan.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Kochin
authors.affiliation: Department of Pathology, Sapporo Medical University, Sapporo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Takasawa
authors.affiliation: Department of Pathology, Sapporo Medical University, Sapporo, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.affiliation: Department of Molecular Therapeutics, Center for Food and Medical Innovation, Hokkaido University, Sapporo, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Department of Oral Surgery, Sapporo Medical University, Sapporo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Miyazaki
authors.affiliation: Department of Pathology, Sapporo Medical University, Sapporo, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.affiliation: Department of Oral Surgery, Sapporo Medical University, Sapporo, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Hiratsuka
authors.affiliation: Department of Pathology, Sapporo Medical University, Sapporo, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D005947:Glucose / Q000172:deficiency; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000276:immunology; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000276:immunology; D009369:Neoplasms / Q000276:immunology*; D013312:Stress, Physiological / Q000276:immunology; D019139:Tumor Escape / Q000276:immunology*; D059016:Tumor Microenvironment / Q000276:immunology; D000097625:HLA-E Antigens
chemical_list: D005947:Glucose; D015395:Histocompatibility Antigens Class I; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D000097625:HLA-E Antigens; C032907:Q surface antigens
keywords: Antigen presentation; Glucose deprivation hypoxia; HLA-E; MHC class I; Microenvironmental stress; Qa-1