Increased Sequence Diversity Coverage Improves Detection of HIV-Specific T Cell Responses

Frahm, Nicole and Kaufmann, Daniel E. and Yusim, Karina and Muldoon, Mark and Kesmir, Can and Linde, Caitlyn H. and Fischer, Will and Allen, Todd M. and Li, Bin and McMahon, Ben H. and Faircloth, Kellie L. and Hewitt, Hannah S. and Mackey, Elizabeth W. and Miura, Toshiyuki and Khatri, Ashok and Wolinsky, Steven and McMichael, Andrew and Funkhouser, Robert K. and Walker, Bruce D. and Brander, Christian and Korber, Bette T. (2007) Increased Sequence Diversity Coverage Improves Detection of HIV-Specific T Cell Responses. Journal of Immunology, 179 (10). pp. 6638-6650. ISSN 0022-1767

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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-γ 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.

Item Type:	Article
Uncontrolled Keywords:	HIV, IFN-γ ELISpot assay, CD4 and CD8 T-cell responses
Subjects:	MSC 2010, the AMS's Mathematics Subject Classification > 92 Biology and other natural sciences
Depositing User:	Dr Mark Muldoon
Date Deposited:	12 Nov 2007
Last Modified:	20 Oct 2017 14:12
URI:	https://eprints.maths.manchester.ac.uk/id/eprint/868

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