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 Watkins, Daniel C. Douek

Research output: Contribution to journalArticle

103 Citations (Scopus)

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-A01 + 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.

Original languageEnglish
Pages (from-to)923-936
Number of pages14
JournalJournal of Experimental Medicine
Volume206
Issue number4
DOIs
StatePublished - Apr 13 2009
Externally publishedYes

Fingerprint

T-Cell Antigen Receptor
T-Lymphocytes
Epitopes
Immunity
Vaccines
Infection
HIV
Population
Viruses
Antigens
AIDS Vaccines
Adaptive Immunity
Virus Diseases
Macaca mulatta
Amino Acid Sequence
Mamu-A 01 antigen

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

Cite this

Price, D. A., Asher, T. E., Wilson, N. A., Nason, M. C., Brenchley, J. M., Metzler, I. S., ... Douek, D. C. (2009). Public clonotype usage identifies protective gag-specific CD8 + t cell responses in SIV infection. Journal of Experimental Medicine, 206(4), 923-936. https://doi.org/10.1084/jem.20081127

Public clonotype usage identifies protective gag-specific CD8 + t cell responses in SIV infection. / Price, David A.; Asher, Tedi E.; Wilson, Nancy A.; Nason, Martha C.; Brenchley, Jason M.; Metzler, Ian S.; Venturi, Vanessa; Gostick, Emma; Chattopadhyay, Pratip K.; Roederer, Mario; Davenport, Miles P.; Watkins, David; Douek, Daniel C.

In: Journal of Experimental Medicine, Vol. 206, No. 4, 13.04.2009, p. 923-936.

Research output: Contribution to journalArticle

Price, DA, Asher, TE, Wilson, NA, Nason, MC, Brenchley, JM, Metzler, IS, Venturi, V, Gostick, E, Chattopadhyay, PK, Roederer, M, Davenport, MP, Watkins, D & Douek, DC 2009, 'Public clonotype usage identifies protective gag-specific CD8 + t cell responses in SIV infection', Journal of Experimental Medicine, vol. 206, no. 4, pp. 923-936. https://doi.org/10.1084/jem.20081127
Price, David A. ; Asher, Tedi E. ; Wilson, Nancy A. ; Nason, Martha C. ; Brenchley, Jason M. ; Metzler, Ian S. ; Venturi, Vanessa ; Gostick, Emma ; Chattopadhyay, Pratip K. ; Roederer, Mario ; Davenport, Miles P. ; Watkins, David ; Douek, Daniel C. / Public clonotype usage identifies protective gag-specific CD8 + t cell responses in SIV infection. In: Journal of Experimental Medicine. 2009 ; Vol. 206, No. 4. pp. 923-936.
@article{b191770b4ed54e3a817847a8e9a68d5d,
title = "Public clonotype usage identifies protective gag-specific CD8 + t cell responses in SIV infection",
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-A01 + 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.",
author = "Price, {David A.} and Asher, {Tedi E.} and Wilson, {Nancy A.} and Nason, {Martha C.} and Brenchley, {Jason M.} and Metzler, {Ian S.} and Vanessa Venturi and Emma Gostick and Chattopadhyay, {Pratip K.} and Mario Roederer and Davenport, {Miles P.} and David Watkins and Douek, {Daniel C.}",
year = "2009",
month = "4",
day = "13",
doi = "10.1084/jem.20081127",
language = "English",
volume = "206",
pages = "923--936",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "4",

}

TY - JOUR

T1 - Public clonotype usage identifies protective gag-specific CD8 + t cell responses in SIV infection

AU - Price, David A.

AU - Asher, Tedi E.

AU - Wilson, Nancy A.

AU - Nason, Martha C.

AU - Brenchley, Jason M.

AU - Metzler, Ian S.

AU - Venturi, Vanessa

AU - Gostick, Emma

AU - Chattopadhyay, Pratip K.

AU - Roederer, Mario

AU - Davenport, Miles P.

AU - Watkins, David

AU - Douek, Daniel C.

PY - 2009/4/13

Y1 - 2009/4/13

N2 - 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-A01 + 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.

AB - 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-A01 + 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.

UR - http://www.scopus.com/inward/record.url?scp=65549116509&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65549116509&partnerID=8YFLogxK

U2 - 10.1084/jem.20081127

DO - 10.1084/jem.20081127

M3 - Article

VL - 206

SP - 923

EP - 936

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 4

ER -