Characterization of Schistosoma mansoni 44.756.8 kDa egg antigens recognized by human monoclonal antibodies which induce protection against experimental infection and proliferation of peripheral blood mononuclear cells from schistosomiasis patients

Hirsch, Cristine; Almeida, Célia A; Doughty, Barbara L.; Góes, Alfredo M.

doi:10.1016/s0264-410x(96)00305-2

Cited by 5 publications

(2 citation statements)

References 26 publications

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“…Bank), the precise identity of most sensitizing egg-stage antigens still remains to be elucidated. Of several potential immunogenic egg components (21,30,42), the most abundant and extensively studied is the Sm-p40 antigen, which is a small heat shock protein with homologies to alpha-crystallins (32). Smp40 is a potent egg immunogen which elicits a strong I-A k restricted Th-1-type response in C3H and CBA mice (7,19,20).…”

Section: Fig 4 Proliferative Responses Of Cd4mentioning

confidence: 99%

Schistosoma mansoniPhosphoenolpyruvate Carboxykinase, a Novel Egg Antigen: Immunological Properties of the Recombinant Protein and Identification of a T-Cell Epitope

et al. 2000

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In schistosomiasis mansoni, hepatic granulomatous inflammation surrounding parasite eggs is mediated by CD4؉ T helper (Th) cells sensitized to schistosomal egg antigens (SEA). We previously showed that a prominent lymphoproliferative response of CD4 ؉ Th cells from schistosome-infected C57BL/6 (BL/6) mice was directed against a 62-kDa component of SEA. A partial amino acid sequence of the 62-kDa component was found to be identical with one present in the enzyme phosphoenolpyruvate carboxykinase (PEPCK). Based on this sequence, a cDNA clone containing the entire coding region of PEPCK was identified, and the full recombinant Schistosoma mansoni PEPCK (rSm-PEPCK) of 626 amino acids was purified from a prokaryotic expression system. rSm-PEPCK strongly stimulated a specific T-cell hybridoma, 4E6, as well as CD4؉ Th cells from SEA-immunized BL/6 mice and from infected BL/6, CBA, and BALB/c mice. In the infected mice, rSm-PEPCK elicited significant gamma interferon production as well as, to a lesser extent, production of interleukin-2 and -5. In BL/6 and BALB/c mice, the CD4 ؉ Th cell response to rSm-PEPCK was greater than that directed against the egg antigen Sm-p40; conversely, CBA mice responded better to Sm-p40 than to Sm-PEPCK. A 12-amino-acid region (residues 398 to 409: DKSKDPKAHPNS) was demonstrated to contain a T-cell epitope; synthetic peptides containing this epitope significantly stimulated specific hybridoma 4E6 and polyclonal CD4؉ Th cells. The identification and characterization of immunogenic egg components will contribute to the understanding and possible control of T-cell-mediated schistosomal disease.The main immunopathological damage in Schistosoma mansoni infection consists of granulomatous inflammation around parasite eggs in the liver and intestines, which may lead to scarring, portal hypertension, hemorrhage, and death (4, 39). There is considerable variation in the overall severity of this disease, both in humans and in mice. Mice of the C3H and CBA strains develop significantly larger egg granulomas than do those of the C57BL/6 (BL/6) strain (9, 15).Granulomatous inflammation is a complex hypersensitivity reaction that involves the recruitment of various cells, the activation of numerous mediators, including cytokines, and the synthesis of matrix proteins. Granuloma formation is known to be strictly dependent on CD4 ϩ T helper (Th) cells specific for schistosomal egg antigens (SEA) (18, 27), and there is strong evidence that it can be mediated by Th-1-and Th-2-type CD4 ϩ Th cells (11,17,33,40,48). The CD4 ϩ Th cells become activated following specific recognition of accessory cell-bound major histocompatibility complex (MHC) class II molecules harboring selected SEA-derived peptides. We previously investigated the nature of the anti-SEA T-cell repertoire by using CD4 ϩ Th cells from infected mice as well as panels of specific T-cell hybridomas. C3H and CBA mice display strong polyclonal T-cell responses to Sm-p40, a demonstrated major egg immunogen in H-2 k mice (7,19,20). By comparison, in B...

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Section: Fig 4 Proliferative Responses Of Cd4mentioning

confidence: 99%

Schistosoma mansoniPhosphoenolpyruvate Carboxykinase, a Novel Egg Antigen: Immunological Properties of the Recombinant Protein and Identification of a T-Cell Epitope

et al. 2000

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“…In contrast to an impressive number of cloned S. mansoni worm antigens (11,27,30,31,35,38), the list of identified S. mansoni antigens preferentially expressed in eggs is still in its beginning stage, although Fig. 1 and 2A suggest several potential immunogenic egg components possibly representing previously reported candidate antigens (17,25,37). Of these, undoubtedly the most abundant component (fraction 15 in Fig.…”

Section: Discussionmentioning

confidence: 86%

A Novel 62-Kilodalton Egg Antigen fromSchistosoma mansoniInduces a Potent CD4⁺T Helper Cell Response in the C57BL/6 Mouse

1999

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In infection with Schistosoma mansoni, hepatic granuloma formation is mediated by CD4 ؉ T helper (Th) cells sensitized to schistosomal egg antigens. There is considerable variation among infected individuals with respect to both severity of disease and the T-cell response to egg antigens. In the BL/6 mouse, the egg granulomas are relatively small and the relevant sensitizing egg antigens are largely unknown. We investigated the CD4 ؉ Th cell response of infected BL/6 mice to egg antigens fractionated by sodium dodecyl sulfatepolyacrylamide gel electrophoresis and found a prominent lymphoproliferative response to be directed against a 62-kDa component. With the aid of a specific T-cell hybridoma, 4E6, the 62-kDa antigen was isolated; following partial digestion with endoproteinase Glu-C, an internal amino acid sequence was found to be identical with one present in the enzyme phosphoenolpyruvate carboxykinase (PEPCK) of the organisms Caenorhabditis elegans and Treponema pallidum and to differ by one residue from PEPCK of various other species. In CD4 ؉ Th cells from 7.5-8.5-week-infected BL/6 mice, the purified 62-kDa molecule elicited a potent proliferative response which, based on cytokine analysis, was of a mixed Th-1 and Th-2 type. Our results reveal a novel egg antigen of particular prominence in the BL/6 mouse and suggest that the immune response in schistosomiasis is a product of sensitization to egg antigens that may vary considerably in immunogenicity from strain to strain.

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Human immune response in schistosomiasis: the role of P24 in the modulation of cellular reactivity to Schistosoma mansoni antigens

et al. 2002

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Characterization of Schistosoma mansoni 44.756.8 kDa egg antigens recognized by human monoclonal antibodies which induce protection against experimental infection and proliferation of peripheral blood mononuclear cells from schistosomiasis patients

Cited by 5 publications

References 26 publications

Schistosoma mansoniPhosphoenolpyruvate Carboxykinase, a Novel Egg Antigen: Immunological Properties of the Recombinant Protein and Identification of a T-Cell Epitope

Schistosoma mansoniPhosphoenolpyruvate Carboxykinase, a Novel Egg Antigen: Immunological Properties of the Recombinant Protein and Identification of a T-Cell Epitope

A Novel 62-Kilodalton Egg Antigen fromSchistosoma mansoniInduces a Potent CD4⁺T Helper Cell Response in the C57BL/6 Mouse

Human immune response in schistosomiasis: the role of P24 in the modulation of cellular reactivity to Schistosoma mansoni antigens

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Characterization of Schistosoma mansoni 44.756.8 kDa egg antigens recognized by human monoclonal antibodies which induce protection against experimental infection and proliferation of peripheral blood mononuclear cells from schistosomiasis patients

Cited by 5 publications

References 26 publications

Schistosoma mansoniPhosphoenolpyruvate Carboxykinase, a Novel Egg Antigen: Immunological Properties of the Recombinant Protein and Identification of a T-Cell Epitope

Schistosoma mansoniPhosphoenolpyruvate Carboxykinase, a Novel Egg Antigen: Immunological Properties of the Recombinant Protein and Identification of a T-Cell Epitope

A Novel 62-Kilodalton Egg Antigen fromSchistosoma mansoniInduces a Potent CD4+T Helper Cell Response in the C57BL/6 Mouse

Human immune response in schistosomiasis: the role of P24 in the modulation of cellular reactivity to Schistosoma mansoni antigens

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A Novel 62-Kilodalton Egg Antigen fromSchistosoma mansoniInduces a Potent CD4⁺T Helper Cell Response in the C57BL/6 Mouse