title: Identification of class I HLA T cell control epitopes for West Nile virus.
abstract: The recent West Nile virus (WNV) outbreak in the United States underscores the importance of understanding human immune responses to this pathogen. Via the presentation of viral peptide ligands at the cell surface, class I HLA mediate the T cell recognition and killing of WNV infected cells. At this time, there are two key unknowns in regards to understanding protective T cell immunity: 1) the number of viral ligands presented by the HLA of infected cells, and 2) the distribution of T cell responses to these available HLA/viral complexes. Here, comparative mass spectroscopy was applied to determine the number of WNV peptides presented by the HLA-A*11:01 of infected cells after which T cell responses to these HLA/WNV complexes were assessed. Six viral peptides derived from capsid, NS3, NS4b, and NS5 were presented. When T cells from infected individuals were tested for reactivity to these six viral ligands, polyfunctional T cells were focused on the GTL9 WNV capsid peptide, ligands from NS3, NS4b, and NS5 were less immunogenic, and two ligands were largely inert, demonstrating that class I HLA reduce the WNV polyprotein to a handful of immune targets and that polyfunctional T cells recognize infections by zeroing in on particular HLA/WNV epitopes. Such dominant HLA/peptide epitopes are poised to drive the development of WNV vaccines that elicit protective T cells as well as providing key antigens for immunoassays that establish correlates of viral immunity.
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Saghar
authors.initials: S
authors.lastname: Kaabinejadian
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Piazza
authors.forename: Curtis P
authors.initials: CP
authors.lastname: McMurtrey
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Vernon
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Cate
authors.forename: Wilfried
authors.initials: W
authors.lastname: Bardet
authors.forename: Fredda B
authors.initials: FB
authors.lastname: Schafer
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Jackson
authors.forename: Diana M
authors.initials: DM
authors.lastname: Campbell
authors.forename: Rico
authors.initials: R
authors.lastname: Buchli
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rinaldo
authors.forename: William H
authors.initials: WH
authors.lastname: Hildebrand
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014901:West Nile Fever / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D014902:West Nile virus / Q000276:immunology*; D055815:Young Adult
chemical_list: D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments