Phagosomes are competent organelles for antigen cross-presentation

Houde, Mathieu; Bertholet, Sylvie; Gagnon, Étienne; Brunet, Sylvain; Goyette, Guillaume; Laplante, Annie; Princiotta, Michael F.; Thibault, Pierre; Sacks, David L.; Desjardins, Michel

doi:10.1038/nature01912

Cited by 639 publications

(576 citation statements)

References 29 publications

Supporting

Mentioning

546

Contrasting

Unclassified

Order By: Relevance

“…Fig. 1d visualizes that upon receptor-mediated endocytosis the CpG-OVA complex becomes translocated to LAMP-1-positive endosomal-lysosomal compartments, previously shown to express TLR9 (14,30) and competence for cross-presentation (8,9). In contrast, cellular uptake of OVA-FITC is poor and only minute amounts of OVA-FITC were found in vesicular structures some of which colocalized with LAMP-1-positive compartments ( Fig.…”

Section: Cpg-ova Conjugates Translocate To the Phagoendosome Of Dcsmentioning

confidence: 99%

Protective CD8 T Cell Immunity Triggered by CpG-Protein Conjugates Competes with the Efficacy of Live Vaccines

Heit

Schmitz

O’Keeffe

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

In contrast to infectious (live) vaccines are those based on subunit Ag that are notoriously poor in eliciting protective CD8 T cell responses, presumably because subunit Ags become insufficiently cross-presented by dendritic cells (DCs) and because the latter need to be activated to acquire competence for cross-priming. In this study, we show that CpG-Ag complexes overcome these limitations. OVA covalently linked to CpG-DNA (CpG-OVA complex), once it is efficiently internalized by DCs via DNA receptor-mediated endocytosis, is translocated to lysosomal-associated membrane protein 1 (LAMP-1)-positive endosomal-lysosomal compartments recently shown to display competence for cross-presentation. In parallel, CpG-OVA complex loaded DCs become activated and acquire characteristics of professional APCs. In vivo, a single s.c. dose of CpG-OVA complex (10 μg of protein) induces primary and secondary clonal expansion/contraction of Ag-specific CD8 T cells similar in kinetics to live vaccines; examples including Listeria monocytogenes genetically engineered to produce OVA (LM-OVA) and two viral vector-based OVA vaccines analyzed. Interestingly, CpG-OVA complex induced almost equal percentages of Ag-specific memory CD8 T cells as did infection with LM-OVA. A single dose vaccination with CpG-OVA complex protected mice against lethal doses of LM-OVA. These data underscore that the synergy imparted by CpG-OVA complex-mediated combined triggering of innate and specific immunity might be key to initiate CD8 T cell-based immunoprotection by synthetic vaccines based on subunit Ag.

show abstract

Section: Cpg-ova Conjugates Translocate To the Phagoendosome Of Dcsmentioning

confidence: 99%

Protective CD8 T Cell Immunity Triggered by CpG-Protein Conjugates Competes with the Efficacy of Live Vaccines

Heit

Schmitz

O’Keeffe

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…In contrast, cell associated or particulate antigens are internalized within phagosomes. These antigens can be transported to the cytosol for class I processing and TAP-dependent cross-presentation or can be degraded into class II peptides by pHdependent lysomal proteases and loaded onto MHC class II within the phagosome (Houde et al, 2003;. Regulation of the pH within the proteosome seems to determine to which route antigen is directed (Savina et al, 2006).…”

Section: Antigen Presenting Cells: the Gateway To Immunity Or Toleranmentioning

confidence: 99%

Harnessing the immune response to treat cancer

et al. 2010

View full text Add to dashboard Cite

It is well established that the immune system has the capacity to attack malignant cells. During malignant transformation cells acquire numerous molecular and biochemical changes that render them potentially vulnerable to immune cells. Yet it is self-evident that a growing tumour has managed to evade these host defence mechanisms. The exact ways in which the immune system interacts with tumour cells and how cancers are able to escape immunological eradication have only recently started to be fully elucidated. Understanding the relationship between the tumour and the anti-tumour immune response and how this can be altered with conventional treatments and immune-targeted therapies is crucial to developing new treatments for patients with cancer. In this review, focusing on the anti-tumour T-cell response, we summarize our understanding of how tumours, cancer treatments and the immune system interact, how tumours evade the immune response and how this process could be manipulated for the benefit of patients with cancer.

show abstract

“…In the cytosol crosspresented antigens can access the proteasome and follow the MHC class I antigen processing and presentation pathway. The stage of endosomal maturation, from which cross-presented antigen is exported, is heavily debated, and early endosomes as well as late endosomes, including some that might even fuse with the ER, have been implicated [7][8][9][10] .…”

Section: T Cells Detect Infected or Transformed Cells Via Antigen Prementioning

confidence: 99%

MHC presentation via autophagy and how viruses escape from it

Gannagé

Münz

2010

Semin Immunopathol

View full text Add to dashboard Cite

T cells detect infected and transformed cells via antigen presentation by major histocompatibility complex (MHC) molecules on the cell surface. For T cell stimulation, these MHC molecules present fragments of proteins that are expressed or taken up by the cell. These fragments are generated by distinct proteolytic mechanisms for presentation on MHC class I molecules to cytotoxic CD8(+) and on MHC class II molecules to helper CD4(+) T cells. Proteasomes are primarily involved in MHC class I ligand and lysosomes, in MHC class II ligand generation. Autophagy delivers cytoplasmic material to lysosomes and, therefore, contributes to cytoplasmic antigen presentation by MHC class II molecules. In addition, it has been recently realized that this process also supports extracellular antigen processing for MHC class II presentation and cross-presentation on MHC class I molecules. Although the exact mechanisms for the regulation of these antigen processing pathways by autophagy are still unknown, recent studies, summarized in this review, suggest that they contribute to immune responses against infections and to maintain tolerance. Moreover, they are targeted by viruses for immune escape and could maybe be harnessed for immunotherapy. These fragments are generated by distinct proteolytic mechanisms for presentation on MHC class I molecules to cytotoxic CD8 + and on MHC class II molecules to helper CD4 + T cells.Proteasomes are primarily involved in MHC class I ligand, and lysosomes in MHC class II ligand generation. Autophagy delivers cytoplasmic material to lysosomes, and, therefore, contributes to cytoplasmic antigen presentation by MHC class II molecules. In addition, it has been recently realized that this process also supports extracellular antigen processing for MHC class II presentation and cross-presentation on MHC class I molecules. Although the exact mechanisms for the regulation of these antigen processing pathways by autophagy are still unknown, recent studies, summarized in this review, suggest that they contribute to immune responses against infections and to maintain tolerance. Moreover, they are targeted by viruses for immune escape, and could maybe be harnessed for immunotherapy. Gannage and Münz 3

show abstract

Phagosomes are competent organelles for antigen cross-presentation

Cited by 639 publications

References 29 publications

Protective CD8 T Cell Immunity Triggered by CpG-Protein Conjugates Competes with the Efficacy of Live Vaccines

Protective CD8 T Cell Immunity Triggered by CpG-Protein Conjugates Competes with the Efficacy of Live Vaccines

Harnessing the immune response to treat cancer

MHC presentation via autophagy and how viruses escape from it

Contact Info

Product

Resources

About