Increased sequence diversity coverage improves detection of HIV-specific T cell responses.
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.
Frahm
Nicole
N
Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
Kaufmann
Daniel E
DE
Yusim
Karina
K
Muldoon
Mark
M
Kesmir
Can
C
Linde
Caitlyn H
CH
Fischer
Will
W
Allen
Todd M
TM
Li
Bin
B
McMahon
Ben H
BH
Faircloth
Kellie L
KL
Hewitt
Hannah S
HS
Mackey
Elizabeth W
EW
Miura
Toshiyuki
T
Khatri
Ashok
A
Wolinsky
Steven
S
McMichael
Andrew
A
Funkhouser
Robert K
RK
Walker
Bruce D
BD
Brander
Christian
C
Korber
Bette T
BT
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*
D010455:Peptides; D014764:Viral Proteins