Navegando por Palavras-chave "T cell epitopes"
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- ItemAcesso aberto (Open Access)Cellular immune response of humans to the circumsporozoite protein of Plasmodium vivax(Instituto Oswaldo Cruz, Ministério da Saúde, 1991-06-01) Rodrigues, Mauricio Martins [UNIFESP]; Dutra, Araripe P.; Yoshida, Nobuko [UNIFESP]; New York University Department of Medical and Molecular Parasitology; Superintendência de Controle de Endemias; Universidade Federal de São Paulo (UNIFESP)The cellular immune response to the circumsporozoite (CS) protein of plasmodium vivax of individuals from malaria-endemic areas of Brazil was studied. We examined the in vitro proliferative response of the peripheral blood mononuclear cells (PBMC) of 22 individuals when stimulated with a CS recombinant protein (rPvCS-2) and two other synthetic peptides based on the sequenceof the P. vivax CS protein. Seven of the individuals from malaria-endemic area displayed an antigen specific in vitro proliferative responseto the recombinant protein PvCS-2 and one out of 6, proliferative response to the peptide 308-320. In contrast, none of the individuals displayed a proliferative reponse when stimulated with the D/A peptide which represent some of the repeated units present in this CS protein. Our study, therefore, provides evidence for the presence, withinthe major surface antigen of P. vivax sporozoites, of epitopes capble to induce proliferation of human PBMC.
- ItemSomente MetadadadosIn Search of a Vaccine for Mouse Allergy: Significant Reduction of Mus m 1 Allergenicity by Structure-Guided Single-Point Mutations(Karger, 2012-01-01) Ferrari, Elena; Breda, Daniela; Longhi, Renato; Vangelista, Luca; Nakaie, Clovis Ryuichi [UNIFESP]; Elviri, Lisa; Casali, Emanuela; Pertinhez, Thelma A.; Spisni, Alberto; Burastero, Samuele E.; Ist Sci San Raffaele; Univ Parma; CNR; Universidade Federal de São Paulo (UNIFESP)Background: Mouse urinary proteins are relevant allergens from mice urine. We used the recombinant protein Mus m 1 as an allergen model to identify if, by altering Mus m 1 architecture via single-point mutations, we could effectively modify its allergenicity. Methods: Based on structural considerations, we synthesized two single-point mutants, Mus m 1-Y120A and Mus m 1-Y120F, which were expected to harbor large structural alterations. Circular dichroism and fluorescence analysis showed significant conformational rearrangements of the aromatic side chains in the internal cavity of Mus m 1-Y120A when compared to Mus m 1-Y120F and Mus m 1. Evaluation of the allergenic potential of the recombinant molecules was performed in vitro with both immunochemical approaches and assays based on the measurement of basophil degranulation. Moreover, to assess the integrity of the T cell epitopes and as an in vitro measure of immunogenicity, we tested the reactivity of T lymphocytes from subjects allergic to mouse urine against proteins and synthetic peptides encompassing the immunodominant linear epitope containing the mutation. Results: We found that the selected point mutation was able to modulate the protein allergenicity, and to severely impair the recognition of Mus m 1 by IgE, while T cell reactivity was fully maintained. Conclusions: in silico predicted, minimum selected structural modifications allowed to design one protein with reduced allergenicity and preserved immunogenicity. Structurally guided mutations can direct the design of proteins with reduced allergenicity which can be used as vaccines for a safer and more effective immunotherapy of allergic disorders. Copyright (C) 2011 S. Karger AG, Basel
- ItemAcesso aberto (Open Access)Leishmania donovani nucleoside hydrolase (NH36) Domains induce T-cell cytokine responses in human Visceral leishmaniasis(Frontiers Media Sa, 2017) Barbosa Santos, Micheli Luize; Nico, Dirlei; de Oliveira, Fabricia Alvisi; Barreto, Aline Silva; Palatnik-de-Sousa, Iam; Carrillo, Eugenia [UNIFESP]; Moreno, Javier; de Luca, Paula Mello; Morrot, Alexandre; Rosa, Daniela Santoro [UNIFESP]; Palatnik, Marcos; Bani-Correa, Cristiane; de Almeida, Roque Pacheco; Palatnik-de-Sousa, Clarisa BeatrizDevelopment of immunoprotection against visceral leishmaniasis (VL) focused on the identification of antigens capable of inducing a Th1 immune response. Alternatively, antigens targeting the CD8 and T-regulatory responses are also relevant in VL pathogenesis and worthy of being included in a preventive human vaccine. We assessed in active and cured patients and VL asymptomatic subjects the clinical signs and cytokine responses to the Leishmania donovani nucleoside hydrolase NH36 antigen and its N-(F1), central (F2) and C-terminal (F3) domains. As markers of VL resistance, the F2 induced the highest levels of IFN-gamma, IL-1 beta, and TNF-a and, together with F1, the strongest secretion of IL-17, IL-6, and IL-10 in DTH+ and cured subjects. F2 also promoted the highest frequencies of CD3(+)CD4(+)IL-2(+)TNF-alpha-IFN-gamma(-), CD3(+)CD4(+)IL-2(+)TNF-alpha+IFN-gamma(-), CD3(+)CD4(+)IL-2(+)TNF-alpha-IFN-gamma(+), and CD3(+)CD4(+)IL-2(+)TNF-alpha+IFN-gamma(+) T cells in cured and asymptomatic subjects. Consistent with this, the IFN-gamma increase was correlated with decreased spleen (R = -0.428, P = 0.05) and liver sizes (R = -0.428, P = 0.05) and with increased hematocrit counts (R = 0.532, P = 0.015) in response to F1 domain, and with increased hematocrit (R = 0.512, P 0.02) and hemoglobin counts (R = 0.434, P = 0.05) in response to F2. Additionally, IL-17 increases were associated with decreased spleen and liver sizes in response to F1 (R = -0.595, P = 0.005) and F2 (R = -0.462, P = 0.04). Conversely, F1 and F3 increased the CD3(+)CD8(+)IL-2(+)TNF-alpha-IFN-gamma(-), CD3(+)CD8(+)IL-2(+)TNF-alpha+IFN-gamma(-), and CD3(+)CD8(+)IL-2(+)TNF-alpha+IFN-gamma(+) T cell frequencies of VL patients correlated with increased spleen and liver sizes and decreased hemoglobin and hematocrit values. Therefore, cure and acquired resistance to VL correlate with the CD4(+)-Th1 and Th-17 T-cell responses to F2 and F1 domains. Clinical VL outcomes, by contrast, correlate with CD8(+) T-cell responses against F3 and F1, potentially involved in control of the early infection. The in silico-predicted NH36 epitopes are conserved and bind to many HL-DR and HLA and B allotypes. No human vaccine against Leishmania is available thus far. In this investigation, we identified the NH36 domains and epitopes that induce CD4(+) and CD8(+) T cell responses, which could be used to potentiate a human universal T-epitope vaccine against leishmaniasis.