title: Improved Transgenic Mouse Model for Studying HLA Class I Antigen Presentation.
abstract: HLA class I (HLA-I) transgenic mice have proven to be useful models for studying human MHC-related immune responses over the last two decades. However, differences in the processing and presentation machinery between humans and mice may have profound effects on HLA-I restricted antigen presentation. In this study, we generated a novel human TAP-LMP (hTAP-LMP) gene cluster transgenic mouse model carrying an intact human TAP complex and two human immunoproteasome LMP subunits, PSMB8/PSMB9. By crossing the hTAP-LMP strain with different HLA-I transgenic mice, we found that the expression levels of human HLA-I molecules, especially the A3 supertype members (e.g., A11 and A33), were remarkably enhanced in corresponding HLA-I/hTAP-LMP transgenic mice. Moreover, we found that humanized processing and presentation machinery increased antigen presentation of HLA-A11-restricted epitopes and promoted the rapid reduction of hepatitis B virus (HBV) infection in HLA-A11/hTAP-LMP mice. Together, our study highlights that HLA-I/hTAP-LMP mice are an improved model for studying antigen presentation of HLA-I molecules and their related CTL responses.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, 100101, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Man
authors.initials: M
authors.lastname: Huang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, 100101, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, 100101, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Guo
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, 100101, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Xundong
authors.initials: X
authors.lastname: Wei
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, 100101, China.|University of Phayao 19 Moo 2 Maeka, Muang Phayao district, Phayao, 56000, Thailand.
authors.forename: Krung
authors.initials: K
authors.lastname: Phiwpan
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, 100101, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, 100101, China.|Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China.
authors.forename: Xuyu
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D000998:Antiviral Agents / Q000494:pharmacology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007109:Immunity / Q000187:drug effects; D026901:Membrane Transport Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D010455:Peptides / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
chemical_list: D000998:Antiviral Agents; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D026901:Membrane Transport Proteins; D010455:Peptides; C107762:tapasin; D046988:Proteasome Endopeptidase Complex