Comprehensive analysis of west nile virus-specific T cell responses in humans.
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.
Lanteri
Marion C
MC
Blood Systems Research Institute, San Francisco, CA 94118, USA.
Heitman
John W
JW
Owen
Rachel E
RE
Busch
Thomas
T
Gefter
Nelly
N
Kiely
Nancy
N
Kamel
Hany T
HT
Tobler
Leslie H
LH
Busch
Michael P
MP
Norris
Philip J
PJ
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*
D010455:Peptides