title: Comprehensive analysis of west nile virus-specific T cell responses in humans.
abstract: BACKGROUND
  Cellular responses have been shown to play a role in immune control and clearance of West Nile virus (WNV) in murine models. However, little is known about the immunogenic regions of the virus or the phenotype of responding T cells in human infection.
  
  
  METHODS
  Frozen peripheral blood mononuclear cells (PBMCs) from 35 WNV-infected blood donors were screened for virus-specific T cell responses by an interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot assay that used 452 overlapping peptides spanning all WNV proteins. More-detailed phenotypic studies were performed on subjects with high-magnitude T cell responses.
  
  
  RESULTS
  In individuals with identified responses, the total number of recognized WNV peptides ranged from 1 to 9 (median, 2 peptides), and the overall magnitude of responses ranged from 50 to 4210 spot-forming cells (SFCs) per 10(6) PBMCs (median, 130 SFCs/10(6) PBMCs). A subset of 8 frequently recognized peptides from the regions of the genome encoding membrane, envelope, and nonstructural 3 and 4b proteins was identified. Phenotypic study of the highest magnitude WNV-specific T cell responses revealed that most were mediated by CD8+ cells that expressed perforin and/or granzyme B.
  
  
  CONCLUSIONS
  These findings are the first to define the breadth and characteristics of the human T cell response to WNV and have implications for candidate vaccine design and evaluation.
authors.affiliation: Blood Systems Research Institute, San Francisco, CA 94118, USA.
authors.forename: Marion C
authors.initials: MC
authors.lastname: Lanteri
authors.forename: John W
authors.initials: JW
authors.lastname: Heitman
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Owen
authors.forename: Thomas
authors.initials: T
authors.lastname: Busch
authors.forename: Nelly
authors.initials: N
authors.lastname: Gefter
authors.forename: Nancy
authors.initials: N
authors.lastname: Kiely
authors.forename: Hany T
authors.initials: HT
authors.lastname: Kamel
authors.forename: Leslie H
authors.initials: LH
authors.lastname: Tobler
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Norris
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014901:West Nile Fever / Q000276:immunology* / Q000821:virology; D014902:West Nile virus / Q000145:classification / Q000276:immunology*
chemical_list: D010455:Peptides