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HIV-1 capture and antigen presentation by dendritic cells: enhanced viral capture does not correlate with better T-Cell activation

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HAL Id: inserm-00731777

https://www.hal.inserm.fr/inserm-00731777

Submitted on 13 Sep 2012

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HIV-1 capture and antigen presentation by dendritic

cells: enhanced viral capture does not correlate with

better T-Cell activation

Maria Rodriguez-Plata, Alejandra Urrutia, Sylvain Cardinaud, Maria Buzon,

Nuria Izquierdo-Useros, Julia Prado, Maria Puertas, Itziar Erkizia,

Pierre-Grégoire Coulon, Samandhy Cedeño, et al.

To cite this version:

Maria Rodriguez-Plata, Alejandra Urrutia, Sylvain Cardinaud, Maria Buzon, Nuria Izquierdo-Useros,

et al.. HIV-1 capture and antigen presentation by dendritic cells: enhanced viral capture does not

correlate with better T-Cell activation. Retrovirology, BioMed Central, 2012, 9 (Suppl 2), pp.P2.

�inserm-00731777�

(2)

P O S T E R P R E S E N T A T I O N

Open Access

HIV-1 capture and antigen presentation by

dendritic cells: enhanced viral capture does not

correlate with better T-Cell activation

M Rodriguez-Plata

1*

, A Urrutia

2

, S Cardinaud

2

, M Buzon

1

, N Izquierdo-Useros

1

, JG Prado

1

, M Puertas

1

, I Erkizia

1

,

P Coulon

2

, S Cedeño

1

, B Clotet

1

, A Moris

3

, J Martinez-Picado

1

From

AIDS Vaccine 2012

Boston, MA, USA. 9-12 September 2012

Background

During HIV-1 infection, dendritic cells (DC) facilitate dis-semination of HIV-1 while trying to trigger adaptive anti-viral immune responses. We examined whether increased HIV-1 capture in DC matured with lipopolysaccharide (LPS) results in more efficient antigen presentation to HIV-1–specific CD4+and CD8+T cells. In order to block the DC-mediated trans-infection of HIV-1 and maximize antigen loading, we also evaluated a non-infectious inte-grase-deficient HIV-1 isolate, the HIVNL4-3∆IN.

Methods

Immature DC (iDC), mature DC (mDC) activated with IL-1b, TNF-a, IL-6, and PGE2 (ITIP) or LPS during viral uptake, and fully mDC matured with ITIP or with LPS for 48 h before viral loading were tested. Antigen presen-tation to HIV-1-specific CD4+and CD8+T cell clones was quantified by IFN-g ELISPOT. DC-associated p24Gag HIV-1 and DC-mediated HIV-1 trans-infection were also evaluated in parallel.

Results

We showed that higher viral capture of DC did not guar-antee better antigen presentation or T-cell activation. Greater HIVNL4-3 uptake by fully LPS-matured DC

resulted in higher viral transmission to target cells but poorer stimulation of HIV-1–specific CD4+and CD8+T cells. Conversely, maturation of DC with LPS during—but not before—viral loading enhanced both I and HLA-II HIV-1–derived antigen presentation. On the other hand, DC maturation with ITIP during viral uptake only

stimulated HIV-1–specific CD8+ T cells. Integrase-deficient HIVNL4-3∆INwas also efficiently captured and

presented by DC through HLA-I and HLA-II pathways, but in absence of viral dissemination.

Conclusion

Hence, DC maturation state, activation stimulus, and time lag between DC maturation and antigen loading impact HIV-1 capture and virus antigen presentation. Our results demonstrate a dissociation between the capacity to cap-ture HIV-1 and to present viral antigens. HIVNL4-3∆IN

seems to be an attractive candidate to be explored. These results provide new insights into DC biology and have implications in the optimization of DC-based immu-notherapy against HIV-1 infection.

Author details

1

AIDS Research Institute IrsiCaixa, Badalona, Spain.2INSERM, UMRS-945, Infection and Immunity, Université Pierre et Marie C, Paris, France.3INSERM,

UMRS-945, Infection and Immunity, Univ. Pierre et Marie Curie, Paris, France. Published: 13 September 2012

doi:10.1186/1742-4690-9-S2-P2

Cite this article as:Rodriguez-Plata et al.: HIV-1 capture and antigen presentation by dendritic cells: enhanced viral capture does not correlate with better T-Cell activation. Retrovirology2012 9(Suppl 2):P2.

1AIDS Research Institute IrsiCaixa, Badalona, Spain

Full list of author information is available at the end of the article Rodriguez-Plata et al. Retrovirology 2012, 9(Suppl 2):P2 http://www.retrovirology.com/content/9/S2/P2

© 2012 Rodriguez-Plata et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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