Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection

David A Price; Tedi E Asher; Nancy A Wilson; Martha C Nason; Jason M Brenchley; Ian S Metzler; Vanessa Venturi; Emma Gostick; Pratip K Chattopadhyay; Mario Roederer; Miles P Davenport; David I Watkins; Daniel C Douek

doi:10.1084/jem.20081127

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Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection

Journal article

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Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection

David A Price, Tedi E Asher, Nancy A Wilson, Martha C Nason, Jason M Brenchley, Ian S Metzler, Vanessa Venturi, Emma Gostick, Pratip K Chattopadhyay, Mario Roederer, …

The Journal of experimental medicine, Vol.206(4), pp.923-936

2009-04-13

DOI: https://doi.org/10.1084/jem.20081127

PMCID: PMC2715115

PMID: 19349463

Abstract

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.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.66 HIV; 1.66.46 HIV-1
Web Of Science research areas: Immunology; Medicine, Research & Experimental
ESI research areas: Immunology

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Title: Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection
Creators: David A Price - Vaccine Research Center, Biostatistics Research Branch, and Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Cardiff CF14 4XN, Wales, UK
Tedi E Asher - Vaccine Research Center, Biostatistics Research Branch, and Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
Nancy A Wilson - Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53711
Martha C Nason - Vaccine Research Center, Biostatistics Research Branch, and Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
Jason M Brenchley - Vaccine Research Center, Biostatistics Research Branch, and Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, Vaccine Research Center, Biostatistics Research Branch, and Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
Ian S Metzler - Vaccine Research Center, Biostatistics Research Branch, and Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
Vanessa Venturi - Centre for Vascular Research, University of New South Wales, Kensington 2052, Sydney, Australia
Emma Gostick - Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Cardiff CF14 4XN, Wales, UK
Pratip K Chattopadhyay - Vaccine Research Center, Biostatistics Research Branch, and Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
Mario Roederer - Vaccine Research Center, Biostatistics Research Branch, and Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
Miles P Davenport - Centre for Vascular Research, University of New South Wales, Kensington 2052, Sydney, Australia
David I Watkins - Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53711
Daniel C Douek - Vaccine Research Center, Biostatistics Research Branch, and Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
Publication Details: The Journal of experimental medicine, Vol.206(4), pp.923-936
Academic Unit: UMMG Department of Pathology
Language: English
Resource Type: Journal article
PMID: 19349463
PMCID: PMC2715115
Record Identifier: 991031598236902976