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

Iglesias, M. C., Almeida, J. R., Fastenackels, S., van Bockel, D. J., Hashimoto, M., Venturi, V., Gostick, E., Urrutia, A., Wooldridge, L., Clement, Mathew, Gras, S., Wilmann, P. G., Autran, B., Moris, A., Rossjohn, Jamie, Davenport, M. P., Takiguchi, M., Brander, C., Douek, D. C., Kelleher, A. D., Price, David and Appay, V. 2011. Escape from highly effective public CD8+ T-cell clonotypes by HIV. Blood 118 (8) , pp. 2138-2149. 10.1182/blood-2011-01-328781

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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 Ag sensitivity, which impart functional advantages and enable effective suppression of HIV replication. The early L268M 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: American Society of Hematology
ISSN: 0006-4971
Date of First Compliant Deposit: 3 January 2018
Date of Acceptance: 27 June 2011
Last Modified: 28 Feb 2018 22:42
URI: http://orca.cf.ac.uk/id/eprint/107858

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