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, Amparo; Ramirez, Maria C.; Soukhanova, Anna; Sigal, Luis J.

doi:10.4049/jimmunol.171.11.5668

Cited by 49 publications

(41 citation statements)

References 28 publications

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“…Recent studies have suggested that cross-priming is dependent on transfer of whole or partially degraded proteins, rather than mature peptides (35)(36)(37)(38). Therefore, we hypothesized that the minigene-expressing vector pDUO would induce specific CD8 ϩ T cells predominantly by direct priming.…”

Section: Discussionmentioning

confidence: 99%

Prime-Boost with Alternating DNA Vaccines Designed to Engage Different Antigen Presentation Pathways Generates High Frequencies of Peptide-Specific CD8+ T Cells

Radcliffe¹,

Roddick²,

Friedmann

et al. 2006

The Journal of Immunology

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The route for presentation of Ag to CD8+ or CD4+ T cells following DNA vaccination is critical for determining outcome, but the pathways involved are unclear. In this study, we compare two different DNA vaccine designs aimed to elicit CD8+ T cell responses against a specific peptide-epitope either by direct- or cross-presentation. Each carries sequences from tetanus toxin (TT) to provide essential CD4+ T cell help. In the first already proven design, the peptide-epitope is fused to the N-terminal domain of fragment C from TT. This appears to act mainly by cross-presentation. In the second design, the peptide-epitope is encoded by a minigene, with induction of Th responses mediated by coexpression of a hybrid invariant chain molecule, incorporating a single determinant from TT (p30) in exchange for class II-associated invariant chain peptide. This design appears to act mainly via direct presentation from transfected APCs. Both vaccines mediated Th-dependent priming of CD8+ T cells in mice, but the kinetics and level of the responses differed markedly, consistent with engagement of distinct pathways of Ag presentation. Importantly, the vaccines could be combined in an alternating prime-boost regime, in either order, generating substantially expanded memory CD8+ T cells, with potent effector function. Taken together, these results demonstrate that vaccination protocols involving different modes of Ag presentation at prime and boost can significantly improve the effectiveness of immunization.

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Section: Discussionmentioning

confidence: 99%

Prime-Boost with Alternating DNA Vaccines Designed to Engage Different Antigen Presentation Pathways Generates High Frequencies of Peptide-Specific CD8+ T Cells

Radcliffe¹,

Roddick²,

Friedmann

et al. 2006

The Journal of Immunology

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show abstract

“…When placed in a suitable cytokine environment (characteristic of an inflammatory response, viral infection, autoimmune syndrome, or cancer and typified by the presence of type 1 IFNs), these cells can be converted into facultative APCs. For example, the MC57g fibroblast cell line acquires the ability to present Ag to T cells (41,47) and produce IFN-␤ when transfected with pOVA (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Potential of Transfected Muscle Cells to Contribute to DNA Vaccine Immunogenicity

Shirota

Petrenko

Hong

et al. 2007

The Journal of Immunology

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The mechanism(s) by which DNA vaccines trigger the activation of Ag-specific T cells is incompletely understood. A series of in vivo and in vitro experiments indicates plasmid transfection stimulates muscle cells to up-regulate expression of MHC class I and costimulatory molecules and to produce multiple cytokines and chemokines. Transfected muscle cells gain the ability to directly present Ag to CD8 T cells through an IFN-regulatory factor 3-dependent process. These findings suggest that transfected muscle cells at the site of DNA vaccination may contribute to the magnitude and/or duration of the immune response initiated by professional APCs.

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“…Cross-priming is a crucial pathway of exogenous antigen presentation on the HLA class I molecules by APCs, enabling antiviral or antitumour responses (den Haan et al 2000;Sigal et al 1999). It has been shown that intact proteins or non-chaperoned proteasome products can be a source of antigens used for cross-presentation (Norbury et al 2004;Serna et al 2003;Shen and Rock 2004). However, these molecules were shown not to be as effective in cross-priming as peptides chaperoned by HSPs (Binder et al 2001;Binder and Srivastava 2005).…”

Section: Introductionmentioning

confidence: 99%

Identification of potential HLA class I and class II epitope precursors associated with heat shock protein 70 (HSPA)

Stocki

Morris

Preisinger

et al. 2010

Cell Stress and Chaperones

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Heat shock protein 70 (HSPA) is a molecular chaperone which has been suggested to shuttle human leukocyte antigen (HLA) epitope precursors from the proteasome to the transporter associated with antigen processing. Despite the reported observations that peptides chaperoned by HSPA are an effective source of antigens for cross-priming, little is known about the peptides involved in the process. In this study, we investigated the possible involvement of HSPA in HLA class I or class II antigen presentation and analysed the antigenic potential of the associated peptides. HSPA was purified from CCRF-CEM and K562 cell lines, and using mass spectrometry techniques, we identified 44 different peptides which were copurified with HSPA. The affinity of the identified peptides to two HSPA isoforms, HSPA1A and HSPA8, was confirmed using a peptide array. Four of the HSPAassociated peptides were matched with 13 previously reported HLA epitopes. Of these 13 peptides, nine were HLA class I and four were HLA class II epitopes. These results demonstrate the association of HSPA with HLA class I and class II epitopes, therefore providing further evidence for the involvement of HSPA in the antigen presentation process.

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

Cited by 49 publications

References 28 publications

Prime-Boost with Alternating DNA Vaccines Designed to Engage Different Antigen Presentation Pathways Generates High Frequencies of Peptide-Specific CD8+ T Cells

Prime-Boost with Alternating DNA Vaccines Designed to Engage Different Antigen Presentation Pathways Generates High Frequencies of Peptide-Specific CD8+ T Cells

Potential of Transfected Muscle Cells to Contribute to DNA Vaccine Immunogenicity

Identification of potential HLA class I and class II epitope precursors associated with heat shock protein 70 (HSPA)

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