A Protective Domain of Heat-Shock Protein 60 from Histoplasma capsulatum

Deepe, George S.; Gibbons, Reta; Brunner, George D.; Gómez, Francisco

doi:10.1093/infdis/174.4.828

Cited by 57 publications

(39 citation statements)

References 12 publications

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“…Subsequent studies revealed that a particular Ag within the extract, heat shock protein 60 (Hsp60), is immunogenic and confers protection against infection (7,8). Moreover, a region of Hsp60 between aa 172 and 443, termed fragment 3 (F3), is the protective domain of this protein (9). Studies have demonstrated Hsp60 to be a potent inducer of cellular immunity and an immunodominant Ag from Hc as well as other pathogenic organisms (10 -13).…”

Section: H Istoplasma Capsulatum (Hc)mentioning

confidence: 99%

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The Protective Immune Response to Heat Shock Protein 60 ofHistoplasma capsulatumIs Mediated by a Subset of Vβ8.1/8.2+ T Cells

Scheckelhoff

Deepe

2002

The Journal of Immunology

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Immunization with recombinant heat shock protein 60 (rHsp60) from Histoplasma capsulatum or a region of the protein designated fragment 3 (F3) confers protection from a subsequent challenge in mice. To determine the T cell repertoire involved in the response to Hsp60, T cell clones from C57BL/6 mice immunized with rHsp60 were generated and examined for Vβ usage by flow cytometry and RT-PCR. Vβ8.1/8.2+ T cells were preferentially expanded; other clones bore Vβ4, -6, or -11. When Vβ8.1/8.2+ cells were depleted in mice, Vβ4+ T cell clones were almost exclusively isolated. Measurement of cytokine production demonstrated that nine of 16 Vβ8.1/8.2+ clones were Th1, while only three of 13 non-Vβ8.1/8.2+ clones were Th1. In mice immunized with rHsp60, depletion of Vβ8.1/8.2+, but not Vβ6+ plus Vβ7+, T cells completely abolished the protective efficacy of Hsp60 to lethal and sublethal challenges. Examination of the TCR revealed that a subset of Vβ8.1/2+ clones that produced IFN-γ and were reactive to F3 shared a common CDR3 sequence, DGGQG. Transfer of these T cell clones into TCR α/β−/− or IFN-γ−/− mice significantly improved survival, while transfer of other Vβ8.1/8.2+ clones that were F3 reactive but were Th2 or clones that were not reactive to F3 but were Th1 did not confer protection. These data indicate that a distinct subset of Vβ8.1/8.2+ T cells is crucial for the generation of a protective response to rHsp60.

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Section: H Istoplasma Capsulatum (Hc)mentioning

confidence: 99%

“…Recombinant Hsp60 and F3 from Hc were generated as described previously (9). Briefly, genes expressing each protein were cloned in to the NdeI and BamHI sites of pET19b.…”

Section: Recombinant Hsp60 and F3 Productionmentioning

confidence: 99%

The Protective Immune Response to Heat Shock Protein 60 ofHistoplasma capsulatumIs Mediated by a Subset of Vβ8.1/8.2+ T Cells

Scheckelhoff

Deepe

2002

The Journal of Immunology

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“…Using Concanavalin A three main glycoproteins of 84, 70 and 58 KDa were identified 17 , its sugar components bind collagen type II, fibronectin and laminin 18 . Other fungi have been shown to produce heat shock proteins (HSP) that could be locally responsible for the effects on the host immune system 12,24 .…”

mentioning

confidence: 99%

Excretion-secretion products and proteases from live Sporothrix schenckii yeast phase: immunological detection and cleavage of human IgG

Rosa

Gezuele

Calegari

et al. 2009

Rev. Inst. Med. trop. S. Paulo

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suMMARYAntigenic preparations from Sporothrix schenckii usually involve materials from mixed cultures of yeast and mycelia presenting cross-reactions with other deep mycoses. We have standardized pure yeast phase with high viability of the cells suitable to obtain specific excretion-secretion products without somatic contaminations. These excretion-secretion products were highly immunogenic and did not produce noticeable cross-reactions in either double immunodiffusion or Western blot. The antigenic preparation consists mainly of proteins with molecular weights between 40 and 70 kDa, some of them with proteolytic activity in mild acidic conditions. We also observed cathepsin-like activity at two days of culture and chymotrypsin-like activity at four days of culture consistent with the change in concentration of different secreted proteins. The proteases were able to cleave different subclasses of human IgG suggesting a sequential production of antigens and molecules that could interact and interfere with the immune response of the host.

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“…nfection with the pathogenic, soil-based fungus, Histoplasma capsulatum (Hc), 3 produces a wide spectrum of disease, ranging from a mild, influenza-like illness to a progressive, disseminated form that can be life-threatening if untreated. The extent of disease induced by Hc can be correlated to the number of fungal particles to which one is exposed.…”

mentioning

confidence: 99%

Vβ6+ T Cells Are Obligatory for Vaccine-Induced Immunity to Histoplasma capsulatum

Deepe

Gibbons

2001

The Journal of Immunology

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We examined TCR usage to a protective fragment of heat shock protein 60 from the fungus, Histoplasma capsulatum. Nearly 90% of T cell clones from C57BL/6 mice vaccinated with this protein were Vβ6+; the remainder were Vβ14+. Amino acid motifs of the CDR3 region from Vβ6+ cells were predominantly IxGGG, IGG, or SxxGG, whereas it was uniformly SFSGG for Vβ14+ clones. Short term T cell lines from Vβ6+-depleted mice failed to recognize Ag, and no T cell clones could be generated. To determine whether Vβ6+ cells were functionally important, we eliminated them during vaccination. Depletion of Vβ6+ cells abrogated protection in vivo and upon adoptive transfer of cells into TCR αβ−/− mice. Transfer of a Vβ6+, but not a Vβ14+, clone into TCR αβ−/− mice prolonged survival. Cytokine generation by Ag-stimulated splenocytes from immunized mice depleted of Vβ6+ cells was similar to that of controls. The efficacy of the Vβ6+ clone was associated with elevated production of IFN-γ, TNF-α, and GM-CSF compared with that of the Vβ14+ clone. More Vβ6+ cells were present in lungs and spleens of TCR αβ−/− on day 3 postinfection compared with Vβ14+ cells. Thus, a single Vβ family was essential for vaccine-induced immunity. Moreover, the mechanism by which Vβ6+ contributed to protective immunity differed between unfractionated splenocytes and T cell clones.

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A Protective Domain of Heat-Shock Protein 60 from Histoplasma capsulatum

Cited by 57 publications

References 12 publications

The Protective Immune Response to Heat Shock Protein 60 ofHistoplasma capsulatumIs Mediated by a Subset of Vβ8.1/8.2+ T Cells

The Protective Immune Response to Heat Shock Protein 60 ofHistoplasma capsulatumIs Mediated by a Subset of Vβ8.1/8.2+ T Cells

Excretion-secretion products and proteases from live Sporothrix schenckii yeast phase: immunological detection and cleavage of human IgG

Vβ6+ T Cells Are Obligatory for Vaccine-Induced Immunity to Histoplasma capsulatum

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