title: Protective T Cell Responses Featured by Concordant Recognition of Middle East Respiratory Syndrome Coronavirus-Derived CD8+ T Cell Epitopes and Host MHC.
abstract: The coordinated recognition of virus-derived T cell epitopes and MHC molecules by T cells plays a pivotal role in cellular immunity-mediated virus clearance. It has been demonstrated that the conformation of MHC class I (MHC I) molecules can be adjusted by the presented peptide, which impacts T cell activation. However, it is still largely unknown whether the conformational shift of MHC I influences the protective effect of virus-specific T cells. In this study, utilizing the Middle East respiratory syndrome coronavirus-infected mouse model, we observed that through the unusual secondary anchor Ile5, a CD8+T cell epitope drove the conformational fit of Trp73on the α1 helix of murine MHC I H-2KdIn vitro renaturation and circular dichroism assays indicated that this shift of the structure did not influence the peptide/MHC I binding affinity. Nevertheless, the T cell recognition and the protective effect of the peptide diminished when we made an Ile to Ala mutation at position 5 of the original peptide. The molecular bases of the concordant recognition of T cell epitopes and host MHC-dependent protection were demonstrated through both crystal structure determination and tetramer staining using the peptide-MHC complex. Our results indicate a coordinated MHC I/peptide interaction mechanism and provide a beneficial reference for T cell-oriented vaccine development against emerging viruses such as Middle East respiratory syndrome coronavirus.
authors.affiliation: College of Laboratory Medicine and Life Sciences, Institute of Medical Virology, Wenzhou Medical University, Wenzhou 325035, China.|Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: William J
authors.initials: WJ
authors.lastname: Liu
authors.affiliation: Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.|Department of Pathogenic Biology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Lan
authors.affiliation: College of Laboratory Medicine and Life Sciences, Institute of Medical Virology, Wenzhou Medical University, Wenzhou 325035, China.|Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Kefang
authors.initials: K
authors.lastname: Liu
authors.affiliation: Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing 100021, China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China.
authors.forename: Shaolian
authors.initials: S
authors.lastname: Wu
authors.affiliation: Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing 100021, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Bao
authors.affiliation: College of Laboratory Medicine and Life Sciences, Institute of Medical Virology, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Haifeng
authors.identifier: 0000-0002-5325-4077
authors.initials: H
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Qihui
authors.initials: Q
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China.
authors.forename: Lingxia
authors.initials: L
authors.lastname: Han
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yan
authors.identifier: 0000-0002-1912-3620
authors.initials: Y
authors.lastname: Chai
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China; and.
authors.forename: Jincun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Songdong
authors.initials: S
authors.lastname: Meng
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing 100021, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
authors.affiliation: College of Laboratory Medicine and Life Sciences, Institute of Medical Virology, Wenzhou Medical University, Wenzhou 325035, China; gaofu@chinacdc.cn tanwj28@163.com.|Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
authors.affiliation: College of Laboratory Medicine and Life Sciences, Institute of Medical Virology, Wenzhou Medical University, Wenzhou 325035, China; gaofu@chinacdc.cn tanwj28@163.com.|Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Tan
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002942:Circular Dichroism; D018352:Coronavirus Infections / Q000276:immunology*; D018360:Crystallography, X-Ray; D004195:Disease Models, Animal; D058501:Enzyme-Linked Immunospot Assay; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005260:Female; D064532:Histocompatibility Antigen H-2D / Q000737:chemistry / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D065207:Middle East Respiratory Syndrome Coronavirus / Q000276:immunology; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D064532:Histocompatibility Antigen H-2D; D014764:Viral Proteins; D014765:Viral Vaccines