Induction of Herpes Simplex Virus gB-Specific Cytotoxic T Lymphocytes in TAP1-Deficient Mice by Genetic Immunization but Not HSV Infection

Paliard, Xavier; Doe, Barbara; Selby, Mark; Hartog, Karin; Lee, Alexander Y.; Burke, Rae Lyn; Walker, Christopher M.

doi:10.1006/viro.2000.0829

Cited by 7 publications

(6 citation statements)

References 44 publications

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“…Although we should bear in mind that our methods may favor activation of cells restricted by HLAs that bind exogenous peptide from endosomal compartments rather than T cells that are specific for TAP-dependent epitopes, TAP-independent epitope presentation pathways or proteins made early during the lytic phase of viral activity should be considered during the design of therapeutic or preventative interventions that invoke T cell responses against HSV. TAP-independent presentation of HSV-derived peptides in mice has been suggested previously [28]. Further confirmation of TAP-dependency on HSV-2 epitope processing and loading in humans is required.…”

Section: Discussionmentioning

confidence: 55%

Diversity in CD8+ T Cell Function and Epitope Breadth Among Persons with Genital Herpes

et al. 2010

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CD8 + T cells are known to be important in clearing herpes simplex virus (HSV) infections. However, investigating the specific antiviral mechanisms employed by HSV-2-specific T cell populations is limited by a lack of reagents such as CD8 + T cell epitopes and specific tetramers. Using a combination of intracellular cytokine staining flow cytometry and ELISpot methods, we functionally characterized peripheral HSV-2-specific CD8 + T cells from peripheral blood mononuclear cell (PBMC) that recognize 14 selected HSV-2 open-reading frames (ORFs) from 55 HSV-2 seropositive persons; within these ORFs, we subsequently identified more than 20 unique CD8 + T cell epitopes. CD8 + T cells to HSV-2 exhibited significant heterogeneity in their functional characteristics, proliferation, production of inflammatory cytokines, and potential to degranulate ex vivo. The diversity in T cell response in these ex vivo assessments offers the potential of defining immune correlates of HSV-2 reactivation in humans.

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Section: Discussionmentioning

confidence: 55%

Diversity in CD8+ T Cell Function and Epitope Breadth Among Persons with Genital Herpes

et al. 2010

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“…The clinical phenotype of TAP-deficient human beings, who have a limited immunodeficiency with chronic respiratory bacterial infections, illustrates that the TAP-independent pathways may be sufficient to allow the control of viral infections. Indeed, in vivo TAPindependent priming of CD8 ϩ T lymphocytes has been demonstrated in TAP-deficient mice (14,(17)(18)(19) and human beings (20). There is a need, however, for quantitative evaluation of the contribution of these supplementary pathways to Ag presentation in vitro and in vivo.…”

Section: Furin-processed Antigens Targeted To the Secretory Routementioning

confidence: 99%

Furin-Processed Antigens Targeted to the Secretory Route Elicit Functional TAP1−/−CD8+ T Lymphocytes In Vivo

Medina

Ramos²,

Iborra³

et al. 2009

The Journal of Immunology

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Most pathogen-derived peptides recognized by CD8+ CTL are produced by proteasomes and delivered to the endoplasmic reticulum by the TAP transporters associated with Ag processing. Alternative proteases also produce antigenic peptides, but their actual relevance is unclear. There is a need to quantify the contribution of these supplementary pathways in vitro and in vivo. A well-defined TAP-independent secretory route of Ag processing involves the trans-Golgi network protease furin. Quantitation of this route by using OVA constructs encoded by vaccinia viruses indicates that it provides approximately one-third of all surface complexes of peptide and MHC class I molecules. Generation of the epitope carboxyl terminus is a dramatic rate-limiting step, since bypassing it increased efficiency by at least 1000-fold. Notably, the secretory construct activated a similar percentage of Ag-specific CD8+ T cells in wild type as in TAP1-deficient mice, which allow only secretory routes but which have a 10- to 20-fold smaller CD8 compartment. Moreover, these TAP1−/− OVA-specific CD8+ T lymphocytes accomplished elimination of epitope-bearing cells in vivo. The results obtained with this experimental system underscore the potential of secretory pathways of MHC class I Ag presentation to elicit functional CD8+ T lymphocytes in vivo and support the hypothesis that noncytosolic processing mechanisms may compensate in vivo for the lack of proteasome participation in Ag processing in persons genetically deficient in TAP and thus contribute to pathogen control.

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“…It is not clear how pDNA immunization results in CD8 ϩ T cell responses, but evidence exists for direct Ag presentation by plasmid-transfected Ag-presenting cells (APC) as well as cross-presentation [2]. In the latter instance, APC take-up exogenous Ag produced by other cell types and process it in a transporter associated with Ag processing (TAP)-dependent endogenous pathway [3]. This cross-presentation process may represent a crucial event.…”

Section: Introductionmentioning

confidence: 99%

Toll-like receptor ligand links innate and adaptive immune responses by the production of heat-shock proteins

Kumaraguru

Pack

Rouse

2003

Journal of Leukocyte Biology

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The report shows that CpG can exert additional adjuvant effects by inducing cells that are normally inferior antigen (Ag)-presenting cells to participate in immune induction by cross-priming. Macrophages (Mphi) exposed to protein Ag in the presence of bioactive CpG DNA released material that induced primary CD8(+) T cell responses in DC-naïve T cell cultures. This cross-priming event was accompanied by up-regulation of the stress protein response as well as inflammatory cytokine expression in treated Mphi. The material released was indicated to contain inducible heat shock protein-70 and epitope peptide, which in turn, were presented by dendritic cells (DCs) to responder T cells. Such an adjuvant effect by CpG may serve to salvage immunogenic material from otherwise inert depot cellular sites and additionally stimulate DCs to effectively cross-prime. The cross-priming, shown also to occur in vivo, may be particularly useful when Ag doses are low and have minimal opportunity for delivery to DCs for consequent direct priming.

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Induction of Herpes Simplex Virus gB-Specific Cytotoxic T Lymphocytes in TAP1-Deficient Mice by Genetic Immunization but Not HSV Infection

Cited by 7 publications

References 44 publications

Diversity in CD8+ T Cell Function and Epitope Breadth Among Persons with Genital Herpes

Diversity in CD8+ T Cell Function and Epitope Breadth Among Persons with Genital Herpes

Furin-Processed Antigens Targeted to the Secretory Route Elicit Functional TAP1−/−CD8+ T Lymphocytes In Vivo

Toll-like receptor ligand links innate and adaptive immune responses by the production of heat-shock proteins

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