Antigen-specific cytotoxic T lymphocytes protect against lethal West Nile virus encephalitis.
Infection with West Nile virus (WNV) causes fatal encephalitis in immunocompromised animals. Previous studies in mice have established that T cell protection is required for clearance of WNV infection from tissues and preventing viral persistence. The current study assessed whether specific WNV peptide epitopes could elicit a cytotoxic T lymphocyte (CTL) response capable of protecting against virus infection. Hidden Markov model analysis was used to identify WNV-encoded peptides that bound the MHC class I proteins K(b) or D(b). Of the 35 peptides predicted to bind MHC class I molecules, one immunodominant CTL recognition peptide was identified in each of the envelope and non-structural protein 4B genes. Addition of these but not control peptides to CD8(+) T cells from WNV-infected mice induced IFN-gamma production. CTL clones that were generated ex vivo lysed peptide-pulsed or WNV-infected target cells in an antigen-specific manner. Finally, adoptive transfer of a mixture of envelope- and non-structural protein 4B-specific CTL to recipient mice protected against lethal WNV challenge. Based on this, we conclude that CTL responses against immundominant WNV epitopes confer protective immunity and thus should be targets for inclusion in new vaccines.
Purtha
Whitney E
WE
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
Myers
Nancy
N
Mitaksov
Vesselin
V
Sitati
Elizabeth
E
Connolly
Janet
J
Fremont
Daved H
DH
Hansen
Ted H
TH
Diamond
Michael S
MS
D019264:Adoptive Transfer; D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D008390:Markov Chains; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D014901:West Nile Fever / Q000276:immunology* / Q000517:prevention & control; D014902:West Nile virus / Q000276:immunology*
D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D014759:Viral Envelope Proteins