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P16-17. Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV suppressive activity

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HAL Id: inserm-00668485

https://www.hal.inserm.fr/inserm-00668485

Submitted on 9 Feb 2012

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P16-17. Antigen sensitivity is a major determinant of

CD8+ T-cell polyfunctionality and HIV suppressive

activity

Jorge Almeida, Delphine Sauce, D Price, Laura Papagno, S Shin, Arnaud

Moris, Martin Larsen, Gianfranco Pancino, Daniel Douek, Brigitte Autran, et

al.

To cite this version:

Jorge Almeida, Delphine Sauce, D Price, Laura Papagno, S Shin, et al.. P16-17. Antigen sensitivity

is a major determinant of CD8+ T-cell polyfunctionality and HIV suppressive activity. AIDS Vaccine

2009, Oct 2009, Paris, France. pp.P246, �10.1186/1742-4690-6-S3-P246�. �inserm-00668485�

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BioMed Central

Page 1 of 1

(page number not for citation purposes)

Retrovirology

Open Access

Poster presentation

P16-17. Antigen sensitivity is a major determinant of CD8+ T-cell

polyfunctionality and HIV suppressive activity

J Almeida, D Sauce, D Price, L Papagno, S Shin, A Moris, M Larsen,

G Pancino, D Douek, B Autran, A Saez-Cirion and V Appay*

Address: INSERM U945, Paris, France * Corresponding author

Background

Induction of effective CD8+ T cells remains a major goal of vaccine strategies against HIV. Recent work suggests that polyfunctionality and HIV suppressive activity are associated with CD8+ T cell efficacy in HIV infected patients, so that generation of CD8+ T cells with such attributes through vaccination is considered highly desir-able. However, the precise determinants of such qualita-tive attributes remain actually poorly understood, which is a clear drawback for rationale vaccine design.

Methods

In order to provide clear insights into the nature of effec-tive CD8+ T cells, we performed a thorough study of CD8+ T cell attributes associated with efficacy in HIV infection at the clonal level. Isolated CD8+ T clonotypes were expanded in vitro and their functional attributes assessed using polychromatic flow cytometry and HIV suppression assays. Observations were confirmed for the CD4+ T cell lineage as well as with ex vivo data from HIV infected donors.

Results

We show here that T cell polyfunctionality is based on a hierarchical induction of distinct functions according to T cell antigen sensitivity, or recognition efficiency, which defines the strength of interaction between the effector cell and its target. Overall, polyfunctionality and HIV sup-pressive activity appear to be directly linked to the level of antigen sensitivity. Highly sensitive CD8+ T cells display

polyfunctional profiles, efficient proliferation and potent HIV suppressive activity.

Conclusion

Antigen sensitivity emerges as a key determinant of CD8+ T cell efficacy in HIV infection. These findings emphasize the importance to focus the design and immunomonitor-ing of candidate vaccines on the induction of T cells with high antigen sensitivity.

from AIDS Vaccine 2009

Paris, France. 19–22 October 2009 Published: 22 October 2009

Retrovirology 2009, 6(Suppl 3):P246 doi:10.1186/1742-4690-6-S3-P246

<supplement> <title> <p>AIDS Vaccine 2009</p> </title> <editor>Anna Laura Ross</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S3-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf</url> </supplement>

This abstract is available from: http://www.retrovirology.com/content/6/S3/P246 © 2009 Almeida et al; licensee BioMed Central Ltd.

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