Escape from highly effective public CD8+ T-cell clonotypes by HIV

Maria Iglesias, Jorge Almeida, Solene Fastenackels, David van Bockel, Masao Hashimoto, Vanessa Venturi, Emma Gostick, Alejandra Urrutia, Linda Wooldridge, Mathew Clement, Stephanie Gras, Pascal Wilmann, Brigitte Autran, Arnaud Moris, Jamie Rossjohn, Miles Davenport, Masafumi Takiguchi, Christian Brander, Daniel Douek, Anthony D KelleherDavid Price, Victor Appay

Research output: Contribution to journalArticleResearchpeer-review

77 Citations (Scopus)

Abstract

Mapping the precise determinants of T-cell efficacy against viruses in humans is a public health priority with crucial implications for vaccine design. To inform this effort, we performed a comprehensive analysis of the effective CD8(+) T-cell clonotypes that constitute responses specific for the HIV p24 Gag-derived KK10 epitope (KRWIILGLNK; residues 263-272) restricted by HLA-B*2705, which are known to confer superior control of viral replication in HIV-infected individuals. Particular KK10-specific CD8(+) T-cell clonotypes, characterized by TRBV4-3/TRBJ1-3 gene rearrangements, were found to be preferentially selected in vivo and shared between individuals. These public clonotypes exhibit high levels of TCR avidity and antigen sensitivity, which impart functional advantages and enable effective suppression of HIV replication. The early L(268)M mutation at position 6 of the KK10 epitope enables the virus to avoid recognition by these highly effective CD8(+) T-cell clonotypes. However, alternative clonotypes with variant reactivity provide flexibility within the overall KK10-specific response. These findings provide refined mechanistic insights into the workings of an effective CD8(+) T-cell response against HIV.
Original languageEnglish
Pages (from-to)2138 - 2149
Number of pages12
JournalBlood
Volume118
Issue number8
DOIs
Publication statusPublished - 2011

Cite this

Iglesias, M., Almeida, J., Fastenackels, S., van Bockel, D., Hashimoto, M., Venturi, V., ... Appay, V. (2011). Escape from highly effective public CD8+ T-cell clonotypes by HIV. Blood, 118(8), 2138 - 2149. https://doi.org/10.1182/blood-2011-01-328781
Iglesias, Maria ; Almeida, Jorge ; Fastenackels, Solene ; van Bockel, David ; Hashimoto, Masao ; Venturi, Vanessa ; Gostick, Emma ; Urrutia, Alejandra ; Wooldridge, Linda ; Clement, Mathew ; Gras, Stephanie ; Wilmann, Pascal ; Autran, Brigitte ; Moris, Arnaud ; Rossjohn, Jamie ; Davenport, Miles ; Takiguchi, Masafumi ; Brander, Christian ; Douek, Daniel ; Kelleher, Anthony D ; Price, David ; Appay, Victor. / Escape from highly effective public CD8+ T-cell clonotypes by HIV. In: Blood. 2011 ; Vol. 118, No. 8. pp. 2138 - 2149.
@article{cea4473b899f4180af001f0864ba025c,
title = "Escape from highly effective public CD8+ T-cell clonotypes by HIV",
abstract = "Mapping the precise determinants of T-cell efficacy against viruses in humans is a public health priority with crucial implications for vaccine design. To inform this effort, we performed a comprehensive analysis of the effective CD8(+) T-cell clonotypes that constitute responses specific for the HIV p24 Gag-derived KK10 epitope (KRWIILGLNK; residues 263-272) restricted by HLA-B*2705, which are known to confer superior control of viral replication in HIV-infected individuals. Particular KK10-specific CD8(+) T-cell clonotypes, characterized by TRBV4-3/TRBJ1-3 gene rearrangements, were found to be preferentially selected in vivo and shared between individuals. These public clonotypes exhibit high levels of TCR avidity and antigen sensitivity, which impart functional advantages and enable effective suppression of HIV replication. The early L(268)M mutation at position 6 of the KK10 epitope enables the virus to avoid recognition by these highly effective CD8(+) T-cell clonotypes. However, alternative clonotypes with variant reactivity provide flexibility within the overall KK10-specific response. These findings provide refined mechanistic insights into the workings of an effective CD8(+) T-cell response against HIV.",
author = "Maria Iglesias and Jorge Almeida and Solene Fastenackels and {van Bockel}, David and Masao Hashimoto and Vanessa Venturi and Emma Gostick and Alejandra Urrutia and Linda Wooldridge and Mathew Clement and Stephanie Gras and Pascal Wilmann and Brigitte Autran and Arnaud Moris and Jamie Rossjohn and Miles Davenport and Masafumi Takiguchi and Christian Brander and Daniel Douek and Kelleher, {Anthony D} and David Price and Victor Appay",
year = "2011",
doi = "10.1182/blood-2011-01-328781",
language = "English",
volume = "118",
pages = "2138 -- 2149",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "8",

}

Iglesias, M, Almeida, J, Fastenackels, S, van Bockel, D, Hashimoto, M, Venturi, V, Gostick, E, Urrutia, A, Wooldridge, L, Clement, M, Gras, S, Wilmann, P, Autran, B, Moris, A, Rossjohn, J, Davenport, M, Takiguchi, M, Brander, C, Douek, D, Kelleher, AD, Price, D & Appay, V 2011, 'Escape from highly effective public CD8+ T-cell clonotypes by HIV', Blood, vol. 118, no. 8, pp. 2138 - 2149. https://doi.org/10.1182/blood-2011-01-328781

Escape from highly effective public CD8+ T-cell clonotypes by HIV. / Iglesias, Maria; Almeida, Jorge; Fastenackels, Solene; van Bockel, David; Hashimoto, Masao; Venturi, Vanessa; Gostick, Emma; Urrutia, Alejandra; Wooldridge, Linda; Clement, Mathew; Gras, Stephanie; Wilmann, Pascal; Autran, Brigitte; Moris, Arnaud; Rossjohn, Jamie; Davenport, Miles; Takiguchi, Masafumi; Brander, Christian; Douek, Daniel; Kelleher, Anthony D; Price, David; Appay, Victor.

In: Blood, Vol. 118, No. 8, 2011, p. 2138 - 2149.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Escape from highly effective public CD8+ T-cell clonotypes by HIV

AU - Iglesias, Maria

AU - Almeida, Jorge

AU - Fastenackels, Solene

AU - van Bockel, David

AU - Hashimoto, Masao

AU - Venturi, Vanessa

AU - Gostick, Emma

AU - Urrutia, Alejandra

AU - Wooldridge, Linda

AU - Clement, Mathew

AU - Gras, Stephanie

AU - Wilmann, Pascal

AU - Autran, Brigitte

AU - Moris, Arnaud

AU - Rossjohn, Jamie

AU - Davenport, Miles

AU - Takiguchi, Masafumi

AU - Brander, Christian

AU - Douek, Daniel

AU - Kelleher, Anthony D

AU - Price, David

AU - Appay, Victor

PY - 2011

Y1 - 2011

N2 - Mapping the precise determinants of T-cell efficacy against viruses in humans is a public health priority with crucial implications for vaccine design. To inform this effort, we performed a comprehensive analysis of the effective CD8(+) T-cell clonotypes that constitute responses specific for the HIV p24 Gag-derived KK10 epitope (KRWIILGLNK; residues 263-272) restricted by HLA-B*2705, which are known to confer superior control of viral replication in HIV-infected individuals. Particular KK10-specific CD8(+) T-cell clonotypes, characterized by TRBV4-3/TRBJ1-3 gene rearrangements, were found to be preferentially selected in vivo and shared between individuals. These public clonotypes exhibit high levels of TCR avidity and antigen sensitivity, which impart functional advantages and enable effective suppression of HIV replication. The early L(268)M mutation at position 6 of the KK10 epitope enables the virus to avoid recognition by these highly effective CD8(+) T-cell clonotypes. However, alternative clonotypes with variant reactivity provide flexibility within the overall KK10-specific response. These findings provide refined mechanistic insights into the workings of an effective CD8(+) T-cell response against HIV.

AB - Mapping the precise determinants of T-cell efficacy against viruses in humans is a public health priority with crucial implications for vaccine design. To inform this effort, we performed a comprehensive analysis of the effective CD8(+) T-cell clonotypes that constitute responses specific for the HIV p24 Gag-derived KK10 epitope (KRWIILGLNK; residues 263-272) restricted by HLA-B*2705, which are known to confer superior control of viral replication in HIV-infected individuals. Particular KK10-specific CD8(+) T-cell clonotypes, characterized by TRBV4-3/TRBJ1-3 gene rearrangements, were found to be preferentially selected in vivo and shared between individuals. These public clonotypes exhibit high levels of TCR avidity and antigen sensitivity, which impart functional advantages and enable effective suppression of HIV replication. The early L(268)M mutation at position 6 of the KK10 epitope enables the virus to avoid recognition by these highly effective CD8(+) T-cell clonotypes. However, alternative clonotypes with variant reactivity provide flexibility within the overall KK10-specific response. These findings provide refined mechanistic insights into the workings of an effective CD8(+) T-cell response against HIV.

UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21734237

U2 - 10.1182/blood-2011-01-328781

DO - 10.1182/blood-2011-01-328781

M3 - Article

VL - 118

SP - 2138

EP - 2149

JO - Blood

JF - Blood

SN - 0006-4971

IS - 8

ER -

Iglesias M, Almeida J, Fastenackels S, van Bockel D, Hashimoto M, Venturi V et al. Escape from highly effective public CD8+ T-cell clonotypes by HIV. Blood. 2011;118(8):2138 - 2149. https://doi.org/10.1182/blood-2011-01-328781