Coupling of HIV-1 antigen to the selective autophagy receptor SQSTM1/p62 promotes T-cell-mediated immunity

17Citations
Citations of this article
24Readers
Mendeley users who have this article in their library.

Abstract

Vaccines aiming to promote T-cell-mediated immune responses have so far showed limited efficacy, and there is a need for novel strategies. Studies indicate that autophagy plays an inherent role in antigen processing and presentation for CD4+ and CD8+ T cells. Here, we report a novel vaccine strategy based on fusion of antigen to the selective autophagy receptor sequestosome 1 (SQSTM1)/p62. We hypothesized that redirection of vaccine antigen from proteasomal degradation into the autophagy pathway would increase the generation of antigen-specific T cells. A hybrid vaccine construct was designed in which the antigen is fused to the C-terminus of p62, a signaling hub, and a receptor that naturally delivers ubiquitinated cargo for autophagic degradation. Fusion of the human immunodeficiency virus-1 antigen Gagp24 to p62 resulted in efficient antigen delivery into the autophagy pathway. Intradermal immunization of mice revealed that, in comparison to Gagp24 delivered alone, fusion to p62 enhanced the number of Gagp24-specific interferon-γ-producing T cells, including CD8+ T cells. The strategy may also have the potential to modulate the antigenic peptide repertoire. Because p62 and autophagy are highly conserved between species, we anticipate this strategy to be a candidate for the development of T-cell-based vaccines in humans.

Cite

CITATION STYLE

APA

Andersen, A. N., Landsverk, O. J., Simonsen, A., Bogen, B., Corthay, A., & Øynebråten, I. (2016). Coupling of HIV-1 antigen to the selective autophagy receptor SQSTM1/p62 promotes T-cell-mediated immunity. Frontiers in Immunology, 7(MAY). https://doi.org/10.3389/fimmu.2016.00167

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free