title: Crystal structure of swine major histocompatibility complex class I SLA-1 0401 and identification of 2009 pandemic swine-origin influenza A H1N1 virus cytotoxic T lymphocyte epitope peptides.
abstract: The presentation of viral epitopes to cytotoxic T lymphocytes (CTLs) by swine leukocyte antigen class I (SLA I) is crucial for swine immunity. To illustrate the structural basis of swine CTL epitope presentation, the first SLA crystal structures, SLA-1 0401, complexed with peptides derived from either 2009 pandemic H1N1 (pH1N1) swine-origin influenza A virus (S-OIV(NW9); NSDTVGWSW) or Ebola virus (Ebola(AY9); ATAAATEAY) were determined in this study. The overall peptide-SLA-1 0401 structures resemble, as expected, the general conformations of other structure-solved peptide major histocompatibility complexes (pMHC). The major distinction of SLA-1 0401 is that Arg(156) has a "one-ballot veto" function in peptide binding, due to its flexible side chain. S-OIV(NW9) and Ebola(AY9) bind SLA-1 0401 with similar conformations but employ different water molecules to stabilize their binding. The side chain of P7 residues in both peptides is exposed, indicating that the epitopes are "featured" peptides presented by this SLA. Further analyses showed that SLA-1 0401 and human leukocyte antigen (HLA) class I HLA-A 0101 can present the same peptides, but in different conformations, demonstrating cross-species epitope presentation. CTL epitope peptides derived from 2009 pandemic S-OIV were screened and evaluated by the in vitro refolding method. Three peptides were identified as potential cross-species influenza virus (IV) CTL epitopes. The binding motif of SLA-1 0401 was proposed, and thermostabilities of key peptide-SLA-1 0401 complexes were analyzed by circular dichroism spectra. Our results not only provide the structural basis of peptide presentation by SLA I but also identify some IV CTL epitope peptides. These results will benefit both vaccine development and swine organ-based xenotransplantation.
authors: Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing 100094, China.
authors: Nianzhi
authors: N
authors: Zhang
authors: Jianxun
authors: J
authors: Qi
authors: Sijia
authors: S
authors: Feng
authors: Feng
authors: F
authors: Gao
authors: Jun
authors: J
authors: Liu
authors: Xiaocheng
authors: X
authors: Pan
authors: Rong
authors: R
authors: Chen
authors: Qirun
authors: Q
authors: Li
authors: Zhaosan
authors: Z
authors: Chen
authors: Xiaoying
authors: X
authors: Li
authors: Chun
authors: C
authors: Xia
authors: George F
authors: GF
authors: Gao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D029043:Ebolavirus / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D055550:Protein Stability; D017385:Sequence Homology; D013552:Swine; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C438668:swine leukocyte antigen