Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 6171K) PDF+supp data (11041K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Price, D. A. Articles by Douek, D. C. Search for Related Content PubMed PubMed Citation Articles by Price, D. A. Articles by Douek, D. C. Social Bookmarking                            What's this?

¹ Vaccine Research Center, ² Biostatistics Research Branch, and ³ Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
⁴ Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Cardiff CF14 4XN, Wales, UK
⁵ Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53711
⁶ Centre for Vascular Research, University of New South Wales, Kensington 2052, Sydney, Australia

CORRESPONDENCE David A. Price: dprice1{at}mail.nih.gov OR Daniel C. Douek: ddouek{at}mail.nih.gov

Despite the pressing need for an AIDS vaccine, the determinants of protective immunity to HIV remain concealed within the complexity of adaptive immune responses. We dissected immunodominant virus-specific CD8⁺ T cell populations in Mamu-A*01⁺ rhesus macaques with primary SIV infection to elucidate the hallmarks of effective immunity at the level of individual constituent clonotypes, which were identified according to the expression of distinct T cell receptors (TCRs). The number of public clonotypes, defined as those that expressed identical TCR β-chain amino acid sequences and recurred in multiple individuals, contained within the acute phase CD8⁺ T cell population specific for the biologically constrained Gag CM9 (CTPYDINQM; residues 181–189) epitope correlated negatively with the virus load set point. This independent molecular signature of protection was confirmed in a prospective vaccine trial, in which clonotype engagement was governed by the nature of the antigen rather than the context of exposure and public clonotype usage was associated with enhanced recognition of epitope variants. Thus, the pattern of antigen-specific clonotype recruitment within a protective CD8⁺ T cell population is a prognostic indicator of vaccine efficacy and biological outcome in an AIDS virus infection.

© 2009 The Rockefeller University Press
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Valentine, L. E., Loffredo, J. T., Bean, A. T., Leon, E. J., MacNair, C. E., Beal, D. R., Piaskowski, S. M., Klimentidis, Y. C., Lank, S. M., Wiseman, R. W., Weinfurter, J. T., May, G. E., Rakasz, E. G., Wilson, N. A., Friedrich, T. C., O'Connor, D. H., Allison, D. B., Watkins, D. I. (2009). Infection with "Escaped" Virus Variants Impairs Control of Simian Immunodeficiency Virus SIVmac239 Replication in Mamu-B*08-Positive Macaques. J. Virol. 83: 11514-11527 [Abstract] [Full Text]  
• Wieckowski, S., Baumgaertner, P., Corthesy, P., Voelter, V., Romero, P., Speiser, D. E., Rufer, N. (2009). Fine Structural Variations of {alpha}{beta}TCRs Selected by Vaccination with Natural versus Altered Self-Antigen in Melanoma Patients. J. Immunol. 183: 5397-5406 [Abstract] [Full Text]  
• Maxmen, A. (2009). HIV, prayer, and vintage cars: Danny Douek talks shop. JEM 206: 1454-1455 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS