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,¶,*
* Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129;
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545;
School of Mathematics, University of Manchester, Manchester, United Kingdom;
Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark;
¶ Theoretical Biology/Bioinformatics, Utrecht University, Utrecht, The Netherlands;
|| Endocrine Unit, Massachusetts General Hospital, Charlestown, MA 02114;
# Department of Medicine, Feinberg School of Medicine, Northwestern University Chicago, IL 60611;
** International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208;
Medical Research Council (MRC) Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom;
* Howard Hughes Medical Institute, Chevy Chase, MD 20815; and
* Santa Fe Institute, Santa Fe, NM 87501
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-
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by Federal funds from the National Institute of Allergy and Infectious Disease and National Institute of Health Contracts Nos. N01-AI-15442 and AI-30024 (to B.D.W.), R01-AI-067077 (to C.B.), R56-AI-071726 (to C.B.), R01-AI-054178 (to T.M.A.), and R21-AI-055421 (to K.Y.). It was also supported by internal directed research funds (LDRD) from the Los Alamos National Laboratory and a Harvard University Center for Acquired Immunodeficiency Syndrome Research grant (to D.E.K).
2 N.F., D.E.K., K.Y., C.B., and B.T.K. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Bette T. Korber, MS K710, T-10, Los Alamos National Laboratory, Los Alamos, NM 87545. E-mail address: btk{at}lanl.gov; or Dr. Christian Brander, Massachusetts General Hospital, AIDS Research Center, 149 13th Street, Room 5234, Charlestown, MA 02129. E-mail address: cbrander{at}partners.org
4 Abbreviations used in this paper: MS, mass spectrometry; OLP, overlapping peptide; GLM, generalized linear model; SFC, spot forming cell; PTE, potential T cell epitope.
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  C. M. Rousseau, M. G. Daniels, J. M. Carlson, C. Kadie, H. Crawford, A. Prendergast, P. Matthews, R. Payne, M. Rolland, D. N. Raugi, et al. HLA Class I-Driven Evolution of Human Immunodeficiency Virus Type 1 Subtype C Proteome: Immune Escape and Viral Load J. Virol., July 1, 2008; 82(13): 6434 - 6446. [Abstract] [Full Text] [PDF]
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