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HIV-infected dendritic cells present endogenous MHC class II–restricted antigens to HIV-specific CD4+ T cells

Coulon, Pierre-Grégoire, Richetta, Clémence, Rouers, Angéline, Blanchet, Fabien P., Urrutia, Alejandra, Guerbois, Mathilde, Piguet, Vincent, Theodorou, Ioannis, Bet, Anne, Schwartz, Olivier, Tangy, Frédéric, Graff-Dubois, Stéphanie, Cardinaud, Sylvain and Moris, Arnaud 2016. HIV-infected dendritic cells present endogenous MHC class II–restricted antigens to HIV-specific CD4+ T cells. Journal of Immunology 197 (2) , pp. 517-532. 10.4049/jimmunol.1600286

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It is widely assumed that CD4+ T cells recognize antigenic peptides (epitopes) derived solely from incoming, exogenous, viral particles or proteins. However, alternative sources of MHC class II (MHC-II)–restricted Ags have been described, in particular epitopes derived from newly synthesized proteins (so-called endogenous). In this study, we show that HIV-infected dendritic cells (DC) present MHC-II–restricted endogenous viral Ags to HIV-specific (HS) CD4+ T cells. This endogenous pathway functions independently of the exogenous route for HIV Ag presentation and offers a distinct possibility for the immune system to activate HS CD4+ T cells. We examined the implication of autophagy, which plays a crucial role in endogenous viral Ag presentation and thymic selection of CD4+ T cells, in HIV endogenous presentation. We show that infected DC do not use autophagy to process MHC-II–restricted HIV Ags. This is unlikely to correspond to a viral escape from autophagic degradation, as infecting DC with Nef- or Env-deficient HIV strains did not impact HS T cell activation. However, we demonstrate that, in DC, specific targeting of HIV Ags to autophagosomes using a microtubule-associated protein L chain 3 (LC3) fusion protein effectively enhances and broadens HS CD4+ T cell responses, thus favoring an endogenous MHC-II–restricted presentation. In summary, in DC, multiple endogenous presentation pathways lead to the activation of HS CD4+ T cell responses. These findings will help in designing novel strategies to activate HS CD4+ T cells that are required for CTL activation/maintenance and B cell maturation.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: American Association of Immunologists
ISSN: 0022-1767
Date of Acceptance: 17 May 2016
Last Modified: 09 Jun 2020 13:30

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