Molecular analysis of herpesviral gene products recognized by protective cytolytic T lymphocytes

Koszinowski, Ulrich H.; Reddehase, Matthias J.; Keil, Günther M.; Volkmer, Hansjürgen; Jonjić, Stipan; Messerle, Martin; Val, Margarita Del; Mutter, Wolfgang; Münch, Konrad; Bühler, Brigitte

doi:10.1016/0165-2478(87)90146-5

Cited by 22 publications

(7 citation statements)

References 45 publications

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“…The immunological significance of early protein recognition has been intensively studied in CMV infections of BALB/c mice, where an IE viral protein, pp89, accounts for the bulk of the CTL response (reviewed in Koszinowski et al, 1987). Immune responses against pp89 alone provide potent protection against infection, an effect mediated principally by MHC class I CD8 + T cells (Jonjic et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

“…In murine cytomegalovirus (CMV) infection, the principal protein recognized by BALB/c CTL is a non-structural immediate early regulatory protein (Koszinowski et al, 1987). The CTL response to human CMV includes structural glycoproteins as well as immediate early gene products but responses to the latter appear to predominate (Borysiewicz et al,I988).…”

Section: Introductionmentioning

confidence: 99%

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Murine cytotoxic T lymphocytes specific for herpes simplex virus type 1 recognize the immediate early protein ICP4 but not ICP0

Martin

Zhu

Silverstein

et al. 1990

Journal of General Virology

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Vaccinia virus recombinants expressing the herpes simplex virus type 1 (HSV-1) genes encoding ICP0 or ICP4 were used to identify the precise target antigen(s) of murine anti-viral cytotoxic T lymphocytes (CTL) specific for the non-structural immediate early proteins. These studies revealed that HSV-l-specific CTL, restricted to class I major histocompatibility complex genes of the H-2 k haplotype but not the H-2 d or H-2 b haplotypes, would lyse autologous cells expressing ICP4. HSV-l-specific CTL derived from various mice strains failed to lyse target cells expressing ICP0. Calculation of the frequencies of H-2k-restricted virusspecific CTL demonstrated that approximately a third of the total HSV-l-specific response was directed against ICP4. Immunization of mice with either recombinant vaccinia virus or transfected L cells expressing ICP4 induced HSV-l-specific lymphoproliferation and delayed hypersensitivity but CTLs were not induced. More importantly, such immunized animals were unable to resist or control a subsequent challenge with virulent HSV-1.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Murine cytotoxic T lymphocytes specific for herpes simplex virus type 1 recognize the immediate early protein ICP4 but not ICP0

Martin

Zhu

Silverstein

et al. 1990

Journal of General Virology

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“…DNA sequence encoding RAAAAAYPHFMPTNLAAAAASRESQC was removed by AvaI and BstXI restriction enzymes (Roche) and replaced by sequences encoding RASIINFEKLSRESQC and RASIINFEKL, respectively. All genes were cloned under the control of the vaccinia early-late promoter 7.5k.rVACV were produced as previously described (25) and DNA sequence confirmed. The recombinant encoding hepatitis B virus secretory protein, rVACVHBe (26), was used as negative control.…”

Section: Recombinant Vaccinia Virusesmentioning

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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“…Depleting CD4 T cells from the transferred cells has little eVect on control of infection and none on the prevention of lethal disease [14,45]. Transferring CD8 T cells alone is as eVective in reducing lung, adrenal gland, and spleen titres as transferring both subsets [40,41,43,45,46]. Depleting CD8 T cells, however, or CD4 and CD8 T cells, results in organ immunopathology, virus replication in all organs tested, and 100% lethality [40,45].…”

Section: Balb/cmentioning

confidence: 99%

MHC class I immune evasion in MCMV infection

Doom

Hill

2008

Med Microbiol Immunol

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Murine cytomegalovirus (MCMV) is a well-studied model of natural beta-herpesvirus infection. However, many questions remain regarding its control by and evasion of the immune response it generates. CD8 and CD4 T cells have both unique and redundant roles in control of the virus that differ based on the immunocompetence of the infected mice. MCMV encodes major histocompatibility complex (MHC) class I immune evasion genes that can have an impact in vitro, but their role in infection of immunocompetent mice has been difficult to identify. This review addresses the evidence for their in vivo function and suggests why they may be evolutionarily conserved.

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Molecular analysis of herpesviral gene products recognized by protective cytolytic T lymphocytes

Cited by 22 publications

References 45 publications

Murine cytotoxic T lymphocytes specific for herpes simplex virus type 1 recognize the immediate early protein ICP4 but not ICP0

Murine cytotoxic T lymphocytes specific for herpes simplex virus type 1 recognize the immediate early protein ICP4 but not ICP0

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

MHC class I immune evasion in MCMV infection

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