title: Increased sequence diversity coverage improves detection of HIV-specific T cell responses.
abstract: The accurate identification of HIV-specific T cell responses is important for determining the relationship between immune response, viral control, and disease progression. HIV-specific immune responses are usually measured using peptide sets based on consensus sequences, which frequently miss responses to regions where test set and infecting virus differ. In this study, we report the design of a peptide test set with significantly increased coverage of HIV sequence diversity by including alternative amino acids at variable positions during the peptide synthesis step. In an IFN-gamma ELISpot assay, these "toggled" peptides detected HIV-specific CD4(+) and CD8(+) T cell responses of significantly higher breadth and magnitude than matched consensus peptides. The observed increases were explained by a closer match of the toggled peptides to the autologous viral sequence. Toggled peptides therefore afford a cost-effective and significantly more complete view of the host immune response to HIV and are directly applicable to other variable pathogens.
authors.affiliation: Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Kaufmann
authors.forename: Karina
authors.initials: K
authors.lastname: Yusim
authors.forename: Mark
authors.initials: M
authors.lastname: Muldoon
authors.forename: Can
authors.initials: C
authors.lastname: Kesmir
authors.forename: Caitlyn H
authors.initials: CH
authors.lastname: Linde
authors.forename: Will
authors.initials: W
authors.lastname: Fischer
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Ben H
authors.initials: BH
authors.lastname: McMahon
authors.forename: Kellie L
authors.initials: KL
authors.lastname: Faircloth
authors.forename: Hannah S
authors.initials: HS
authors.lastname: Hewitt
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Mackey
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miura
authors.forename: Ashok
authors.initials: A
authors.lastname: Khatri
authors.forename: Steven
authors.initials: S
authors.lastname: Wolinsky
authors.forename: Andrew
authors.initials: A
authors.lastname: McMichael
authors.forename: Robert K
authors.initials: RK
authors.lastname: Funkhouser
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
mesh_terms: D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques / Q000191:economics; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D010455:Peptides; D014764:Viral Proteins