title: A computational method for identification of vaccine targets from protein regions of conserved human leukocyte antigen binding.
abstract: BACKGROUND
  Computational methods for T cell-based vaccine target discovery focus on selection of highly conserved peptides identified across pathogen variants, followed by prediction of their binding of human leukocyte antigen molecules. However, experimental studies have shown that T cells often target diverse regions in highly variable viral pathogens and this diversity may need to be addressed through redefinition of suitable peptide targets.
  
  
  METHODS
  We have developed a method for antigen assessment and target selection for polyvalent vaccines, with which we identified immune epitopes from variable regions, where all variants bind HLA. These regions, although variable, can thus be considered stable in terms of HLA binding and represent valuable vaccine targets.
  
  
  RESULTS
  We applied this method to predict CD8+ T-cell targets in influenza A H7N9 hemagglutinin and significantly increased the number of potential vaccine targets compared to the number of targets discovered using the traditional approach where low-frequency peptides are excluded.
  
  
  CONCLUSIONS
  We developed a webserver with an intuitive visualization scheme for summarizing the T cell-based antigenic potential of any given protein or proteome using human leukocyte antigen binding predictions and made a web-accessible software implementation freely available at http://met-hilab.cbs.dtu.dk/blockcons/.
authors.forename: Lars R
authors.initials: LR
authors.lastname: Olsen
authors.forename: Christian
authors.initials: C
authors.lastname: Simon
authors.forename: Ulrich J
authors.initials: UJ
authors.lastname: Kudahl
authors.forename: Frederik O
authors.initials: FO
authors.lastname: Bagger
authors.forename: Ole
authors.initials: O
authors.lastname: Winther
authors.forename: Ellis L
authors.initials: EL
authors.lastname: Reinherz
authors.forename: Guang L
authors.initials: GL
authors.lastname: Zhang
authors.forename: Vladimir
authors.initials: V
authors.lastname: Brusic
mesh_terms: D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods*; D017124:Conserved Sequence; D018604:Epitope Mapping; D006680:HLA Antigens / Q000737:chemistry* / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000276:immunology; D008969:Molecular Sequence Data; D011485:Protein Binding; D012984:Software; D014612:Vaccines / Q000276:immunology*
chemical_list: D006680:HLA Antigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014612:Vaccines