tetano
Editor, Senior Moderator
J Virol. 2011 Sep 7. [Epub ahead of print]
Crystal structure of swine MHC class I SLA-1*0401 and identification of 2009-pandemic swine-origin influenza A H1N1 virus (S-OIV) CTL epitope-peptides.
Zhang N, Qi J, Feng S, Gao F, Liu J, Pan X, Chen R, Li Q, Chen Z, Li X, Xia C, Gao GF.
Source
Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing 100094, China.
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), have been determined in this study. The overall peptide-SLA-1*0401 structures represent, as expected, the general mode of other structure-solved peptide major histocompatibility complexes (pMHC). The major distinction of the SLA-1*0401 is that Arg(156) has a "one-ballot veto" function in peptide binding, due to its flexible side chain. Both peptides 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 peptidesis exposed, making the epitopes as 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 the cross-species epitope presentation. CTL epitope-peptides derived from 2009 pandemic S-OIV has been screened and evaluated by 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 CD 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.
PMID:
21900158
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21900158
Crystal structure of swine MHC class I SLA-1*0401 and identification of 2009-pandemic swine-origin influenza A H1N1 virus (S-OIV) CTL epitope-peptides.
Zhang N, Qi J, Feng S, Gao F, Liu J, Pan X, Chen R, Li Q, Chen Z, Li X, Xia C, Gao GF.
Source
Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing 100094, China.
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), have been determined in this study. The overall peptide-SLA-1*0401 structures represent, as expected, the general mode of other structure-solved peptide major histocompatibility complexes (pMHC). The major distinction of the SLA-1*0401 is that Arg(156) has a "one-ballot veto" function in peptide binding, due to its flexible side chain. Both peptides 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 peptidesis exposed, making the epitopes as 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 the cross-species epitope presentation. CTL epitope-peptides derived from 2009 pandemic S-OIV has been screened and evaluated by 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 CD 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.
PMID:
21900158
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21900158