Macrophages and Dendritic Cells Use the Cytosolic Pathway to Rapidly Cross-Present Antigen from Live, Vaccinia-Infected Cells

Ramirez, Maria C.; Sigal, Luis J.

doi:10.4049/jimmunol.169.12.6733

Cited by 94 publications

(78 citation statements)

References 60 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is likely that the majority of the CD11c À populations are Mø that were reported to cross-present antigens in a comparable manner to DC [27,28]. Interestingly, NP396 was the best epitope to be cross-presented by the CD11c 1 cell, which confirms our observation in vitro.…”

Section: Discussionsupporting

confidence: 88%

The outcome of cross‐priming during virus infection is not directly linked to the ability of the antigen to be cross‐presented

et al. 2010

View full text Add to dashboard Cite

The initiation of CD8 1 T cell (CTL) immune responses can occur via cross-priming. Recent data suggested a relationship between cross-presentation and immunodominance of epitope-specific T cells. To test this association, we evaluated the efficacy of crosspresentation for several virus epitopes in vitro and examined if this can be extrapolated in vivo. Employing lymphocytic choriomeningitis virus (LCMV), we demonstrate that the cross-presentation and cross-priming of LCMV antigens were dominated by NP396, but not NP205 when analyzing the LCMV-NP. Although with LCMV-GP, cross-presentation was dominated by GP276, and cross-priming was dominated by GP33. Importantly, although NP396 was significantly more efficient than GP33 in cross-presentation, cross-priming of their specific CTL was comparable. In a subsequent virus challenge after cross-priming, GP33-specific CTL dominated the response. Accordingly, based on our data, the ability of viral epitopes to be cross-presented in vitro does not entirely reflect what would occur in cross-priming. Thus, weak cross-presenting antigens may still cross-prime an efficient CTL response depending on other in vivo elements such as the naïve T-cell precursor frequencies.

show abstract

Section: Discussionsupporting

confidence: 88%

The outcome of cross‐priming during virus infection is not directly linked to the ability of the antigen to be cross‐presented

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Interestingly, they also found that transgenic mice expressing a mutant form of H2-K b lacking tyrosine in this position mounted reduced CTL responses to two immunodominant viral epitopes, and DC from these mice did not process and present OVA in vitro. They did not investigate where processing occurred but, to accommodate data in similar systems showing inhibition by drugs that block proteasomes, discussed the possibility of it taking place in phagosomes [29,30].…”

Section: Discussionmentioning

confidence: 99%

Alternative processing for MHC class I presentation by immature and CpG‐activated dendritic cells

Chen

Jondal

2004

Eur J Immunol

View full text Add to dashboard Cite

Exogenous proteins can be processed by antigen-presenting cells for the generation of MHC class I-restricted T cell responses. Where this occurs is not clear, although both transfer of internalized antigen into the cytosol and alternative processing in endolysosomes and phagosomes have been reported. Here we have studied the capacity of bone marrowderived mouse myeloid dendritic cells (DC) to process the OVA protein for peptide presentation by H2-K b . We have found that immature DC (iDC), both wild-type and transporter associated with antigen processing (TAP)-deficient cells, can transiently process OVA in a pathway which is resistant to inhibitors of the classical MHC class I pathway including the Golgi inhibitor Brefeldin A (BFA) and the proteasome inhibitor lactacystin. This alternative pathway is not found in subcultured DC with an intermediate maturity (imDC) or in resting, IL-3 expanded macrophages but can be re-expressed in imDC if these are activated by an immunostimulatory CpG oligonucleotide. Both iDC and CpG-activated DC were found to process OVA by regurgitation. In addition, we found that iDC secrete proteolytic enzymes into the supernatant, which can process OVA in the extracellular phase. These results suggest that multiple pathways exist for the processing of exogenous protein antigens into MHC class Ibinding peptides.

show abstract

“…We have previously used a novel cross-presentation assay (15) to demonstrate that primary H-2 b M and DC efficiently crosspresent the K b -restricted epitope 258 -265 of chicken OVA (386 aa) acquired from A9-T7 cells at early stages of vaccinia virus infection and expressed within the cytosolic fragment 197-386 (15). However, whether the Ag transferred from donor cells to pAPC is the whole 197-386 translation product, the 258 -265 mature epitope, or an intermediate fragment was not explored.…”

Section: Resultsmentioning

confidence: 99%

“…B3Z responder cells (10 5 ) were added to each well, and incubated for additional 18 -24 h to allow for the activation of the hybridoma and production of ␤-gal. ␤-gal activity, was determined with the Galactostar chemiluminescent kit (Tropix; Applied Biosystems, Foster City, CA) as before (15).…”

Section: Ag Presentation Assaysmentioning

confidence: 99%

Cutting Edge: Efficient MHC Class I Cross-Presentation during Early Vaccinia Infection Requires the Transfer of Proteasomal Intermediates between Antigen Donor and Presenting Cells

Serna

Ramirez

Soukhanova

et al. 2003

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Priming of CD8+ T cells requires presentation of short peptides bound to MHC class I molecules of professional APCs. Cross-presentation is a mechanism whereby professional APC present on their own MHC class I molecules peptides derived from degradation of Ags synthesized by other Ag “donor cells.” The mechanism of cross-presentation is poorly understood, and the nature of the transferred Ag is unknown. In this report, we demonstrate that the bulk of a cross-presented Ag transferred from donor cells recently infected with vaccinia virus are proteasomal products that are susceptible to peptidases within the donor cell cytosol and not full-length proteins or mature epitopes either free or bound to chaperones.

show abstract

Macrophages and Dendritic Cells Use the Cytosolic Pathway to Rapidly Cross-Present Antigen from Live, Vaccinia-Infected Cells

Cited by 94 publications

References 60 publications

The outcome of cross‐priming during virus infection is not directly linked to the ability of the antigen to be cross‐presented

The outcome of cross‐priming during virus infection is not directly linked to the ability of the antigen to be cross‐presented

Alternative processing for MHC class I presentation by immature and CpG‐activated dendritic cells

Cutting Edge: Efficient MHC Class I Cross-Presentation during Early Vaccinia Infection Requires the Transfer of Proteasomal Intermediates between Antigen Donor and Presenting Cells

Contact Info

Product

Resources

About