title: Structural Illumination of Equine MHC Class I Molecules Highlights Unconventional Epitope Presentation Manner That Is Evolved in Equine Leukocyte Antigen Alleles.
abstract: MHC class I (MHC I)-restricted virus-specific CTLs are implicated as critical components in the control of this naturally occurring lentivirus and in the protective immune response to the successfully applied attenuated equine infectious anemia virus vaccine in the horse. Nevertheless, the structural basis for how the equine MHC I presents epitope peptides remains unknown. In this study, we investigated the binding of several equine infectious anemia virus-derived epitope peptides by the ability to refold recombinant molecules and by thermal stability, and then by determining the x-ray structure of five peptide-MHC I complexes: equine MHC class I allele (Eqca)-N*00602/Env-RW12, Eqca-N*00602/Gag-GW12, Eqca-N*00602/Rev-QW11, Eqca-N*00602/Gag-CF9, and Eqca-N*00601/Gag-GW12. Although Eqca-N*00601 and Eqca-N*00602 differ by a single amino acid, Eqca-N*00601 exhibited a drastically different peptide presentation when binding a similar CTL epitope, Gag-GW12; the result makes the previously reported function clear to be non-cross-recognition between these two alleles. The structures plus Eqca-N*00602 complexed with a 9-mer peptide are particularly noteworthy in that we illuminated differences in apparent flexibility in the center of the epitope peptides for the complexes with Gag-GW12 as compared with Env-RW12, and a strict selection of epitope peptides with normal length. The featured preferences and unconventional presentations of long peptides by equine MHC I molecules provide structural bases to explain the exceptional anti-lentivirus immunity in the horse. We think that the beneficial reference points could serve as an initial platform for other human or animal lentiviruses.
authors.affiliation: Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta T6G 2R3, Canada;
authors.forename: Shugang
authors.identifier: http://orcid.org/0000-0002-2027-8523
authors.initials: S
authors.lastname: Yao
authors.affiliation: Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; and.
authors.forename: Jun
authors.identifier: http://orcid.org/0000-0003-3605-4070
authors.initials: J
authors.lastname: Liu
authors.affiliation: Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; and.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China;
authors.forename: Rong
authors.identifier: http://orcid.org/0000-0002-6716-0071
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China;
authors.forename: Nianzhi
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China;
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China;
authors.forename: Junya
authors.identifier: http://orcid.org/0000-0003-1549-7526
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China;
authors.forename: Yanan
authors.identifier: http://orcid.org/0000-0001-8326-2492
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; and.
authors.forename: George Fu
authors.initials: GF
authors.lastname: Gao
authors.affiliation: Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, China Agricultural University, Beijing 100193, China xiachun@cau.edu.cn.
authors.forename: Chun
authors.identifier: http://orcid.org/0000-0002-3444-0624
authors.initials: C
authors.lastname: Xia
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D018360:Crystallography, X-Ray; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D004859:Equine Infectious Anemia / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006736:Horses / Q000276:immunology*; D004860:Infectious Anemia Virus, Equine / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I