scholarly journals Mapping of the T-Cell Epitope in the Major 43-Kilodalton Glycoprotein of Paracoccidioides brasiliensisWhich Induces a Th-1 Response Protective against Fungal Infection in BALB/c Mice

1998 ◽  
Vol 66 (2) ◽  
pp. 786-793 ◽  
Author(s):  
Carlos P. Taborda ◽  
Maria A. Juliano ◽  
Rosana Puccia ◽  
Marcello Franco ◽  
Luiz R. Travassos
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Cellular Immune Response ◽  
Cell Epitope ◽  
Delayed Type Hypersensitivity ◽  
Computer Assisted ◽  
T Cell Epitope ◽  
Ifn Γ ◽  
Cellular Immune ◽  
Th 1

ABSTRACT The 43-kDa glycoprotein of Paracoccidioides brasiliensis is the major diagnostic antigen of paracoccidioidomycosis, the prevalent systemic mycosis of Latin America. Apart from eliciting high antibody titers, gp43 is also immunodominant in delayed-type hypersensitivity reactions in infected animals and humans. The cellular immune response in mice to gp43 administered in complete Freund’s adjuvant involves CD4+Th-1 lymphocytes, secreting gamma interferon (IFN-γ) and interleukin 2 (IL-2) but not IL-4 and IL-10. The T-cell epitope of this antigen was mapped to a 15-amino-acid peptide (P10) based on lymphoproliferations with primed cells from three different haplotypes and on a computer-assisted protein analysis. The structural requirements of the T-cell epitope were determined by assaying a series of P10 analogous and truncated peptides. Only 12-mer or longer sequences were active, confirming presentation by major histocompatibility complex II. The HTLAIR inner core of P10 is the essential domain of the epitope, with various flanking regions possible. Immunization of mice with both gp43 and P10 led to vigorous protection against intratracheal challenge by virulent P. brasiliensis, with a >200-fold decrease in lung CFU and halting of dissemination to the spleen and liver. The protective effect of P10 is mainly attributed to an IFN-γ-mediated cellular immune response. Unlike gp43, which induces an antibody response compatible with both Th-1 and Th-2 activation in infected BALB/c mice, P10 does not induce a humoral response. Protection by gp43 and P10 was characterized by a few well-demarcated lung granulomas with numerous nonviable yeast forms or resolved lesions with no detectable fungal cells.

scholarly journals Identification of Murine H2-Dd- and H2-Ab-Restricted T-Cell Epitopes on a Novel Protective Antigen, MPT51, of Mycobacterium tuberculosis

2004 ◽  
Vol 72 (7) ◽  
pp. 3829-3837 ◽  
Author(s):  
Mina Suzuki ◽  
Taiki Aoshi ◽  
Toshi Nagata ◽  
Yukio Koide
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Protective Antigen ◽  
Cell Epitope ◽  
Cell Subset ◽  
Cell Phenotype ◽  
Computer Assisted ◽  
T Cell Epitope ◽  
Color Flow ◽  
Ifn Γ

ABSTRACT Both CD4+ type 1 helper T (Th1) cells and CD8+ cytotoxic T lymphocytes (CTL) play pivotal roles in protection against Mycobacterium tuberculosis infection. Here, we identified Th1 and CTL epitopes on a novel protective antigen, MPT51, in BALB/c and C57BL/6 mice. Mice were immunized with plasmid DNA encoding MPT51 by using a gene gun, and gamma interferon (IFN-γ) production from the immune spleen cells was analyzed in response to a synthetic overlapping peptide library covering the mature MPT51 sequence. In BALB/c mice, only one peptide, p21-40, appeared to stimulate the immune splenocytes to produce IFN-γ. Flow cytometric analysis with intracellular IFN-γ and the T-cell phenotype revealed that the p21-40 peptide contains an immunodominant CD8+ T-cell epitope. Further analysis with a computer-assisted algorithm permitted identification of a T-cell epitope, p24-32. In addition, a major histocompatibility complex class I stabilization assay with TAP2-deficient RMA-S cells transfected with Kd, Dd, or Ld indicated that the epitope is presented by Dd. Finally, we proved that the p24-32/Dd complex is recognized by IFN-γ-producing CTL. In C57BL/6 mice, we observed H2-Ab-restricted dominant and subdominant Th1 epitopes by using T-cell subset depletion analysis and three-color flow cytometry. The data obtained are useful for analyzing the role of MPT51-specific T cells in protective immunity and for designing a vaccine against M. tuberculosis infection.

scholarly journals Characterization of Non-Conserved HLA-A*0201 Binding T cell Epitopes of JC Virus T Antigen

2008 ◽  
Vol 1 ◽  
pp. VRT.S957
Author(s):  
Jongming Li ◽  
John L. Wagner ◽  
Bijoyesh Mookerjee
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Cytotoxic T Lymphocytes ◽  
Jc Virus ◽  
Cell Epitope ◽  
T Antigen ◽  
Bk Virus ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Cellular Immune

JC virus-specific CD8+ cytotoxic T lymphocytes are associated with a favorable outcome in patients with progressive multifocal leukoencephalopathy. However, very few JC virus T cell epitopes restricted to MHC class I have been defined. Of the two HLA-A*0201-restricted JCV epitopes, VP1p36 and VP1p100, studies have shown that they are conserved T cell epitopes of polyomaviruses. The cross-recognition associated to these epitopes has complicated the efforts of understanding the dynamics of immune response to JC virus. Based on the previously identified HLA-A*0201 binding T cell epitope of Simian virus 40 T antigen P281–289 (KCDDVLLLL) and BK virus T antigen P558–566 (SLQNSEFLL), T cell epitopes of JC Virus T antigen P282–290 (KCEDVFLLM) and P557–565 (SLSCSEYLL) were identified. In this report, we demonstrated that JC Virus P282–290 and P557–565 were able to stimulate T cell responses in healthy donors’ PBMCs and CD8+ cytotoxic T lymphocytes raised with both peptides could recognize and lyse their targets. Most importantly, there were no T cell cross-recognitions between JC Virus, BK Virus and SV40 virus. Therefore, JCV T-ag epitopes P282–290 and P557–565 could be better antigen epitopes compared to VP1p36 and VP1p100 to study the dynamics of cellular immune response to JCV in PML patients. In addition, as a HLA-A*0201 binding T cell epitope, both peptides could be a valuable component of immunotherapies aiming at increasing the cellular immune response against JCV for the treatment of progressive multifocal leukoencephalopathy.

scholarly journals CD4+ T cells induced by virus-like particles expressing a major T cell epitope down-regulate IL-5 production in an ongoing immune response to Der p 1 independently of IFN-γ production

1999 ◽  
Vol 11 (12) ◽  
pp. 1927-1934 ◽  
Author(s):  
Sandra Hirschberg ◽  
Guy T. Layton ◽  
Stephen J. Harris ◽  
Nigel Savage ◽  
Margaret J. Dallman ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cell Epitope ◽  
T Cell Epitope ◽  
Virus Like Particles ◽  
Der P 1 ◽  
Ifn Γ

Effect of Hypertonic Saline Infusion on Postoperative Cellular Immune Function

2004 ◽  
Vol 100 (5) ◽  
pp. 1108-1118 ◽  
Author(s):  
Jens A. Kølsen-Petersen ◽  
Jens-Ole D. Nielsen ◽  
Else M. Tonnesen
Keyword(s):  
Immune Response ◽  
Immune Function ◽  
Hypertonic Saline ◽  
Cellular Immune Response ◽  
Killer Cell ◽  
Cell Activity ◽  
Abdominal Hysterectomy ◽  
Delayed Type Hypersensitivity ◽  
Laboratory Animals ◽  
Cellular Immune

Background Previous studies found hypertonicity to affect immune responses in intact laboratory animals and in human blood cell cultures. In this study, the authors investigated the cellular immune response to surgery after preoperative infusion of hypertonic saline in humans. Methods Sixty-two women scheduled to undergo abdominal hysterectomy were randomly assigned to single-blinded infusion of 4 ml/kg NaCl, 7.5%; 4 ml/kg NaCl, 0.9%; or 32 ml/kg NaCl, 0.9%, over 20 min. Blood was collected at baseline, during surgery, and 1, 24, and 48 h after surgery for the determination of leukocyte and differential counts, flow cytometric phenotyping of mononuclear cells, and natural killer cell activity against K 562 tumor cells. Phytohemagglutinin-induced lymphocyte proliferation, plasma elastase, and neutrophil chemotaxis were measured at the same time points except during surgery. The authors tested cell-mediated immune function in vivo by delayed-type hypersensitivity reaction in the skin. Results Surgery induced well-known changes in the cellular immune response, which were unrelated to the tonicity or volume of the infused fluids. Conclusion Infusion of a clinically relevant dose of hypertonic saline did not seem to modify the postoperative cellular immune response after elective abdominal hysterectomy.

scholarly journals Corrective effects of original bioflavonoid complex in the cyclophosphamide-induced immunity disorders

2021 ◽  
Vol 22 (6) ◽  
pp. 1111-1120
Author(s):  
I. A. Goldina ◽  
E. V. Markova ◽  
I. A. Orlovskaya ◽  
L. B. Toporkova ◽  
V. A. Kozlov
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Cellular Immune Response ◽  
Proliferative Activity ◽  
Lymphoid Organs ◽  
Delayed Type Hypersensitivity ◽  
Relative Mass ◽  
Hematopoietic Progenitors ◽  
Hematopoietic Stem ◽  
Cellular Immune

Our aim was to evaluate immunomodulatory properties of an original bioflavonoid complex in experimental immune disturbances induced by cyclophosphamide (Cy). We have studied morphometric indexes of thymus and spleen, as well as blood leukocyte counts, cell proliferative activity in lymphoid organs, delayed hypersensitivity responses to T cell-dependent antigen, along with differentiation activity of bone marrow stem cells in experimental animals during Cy-induced immune suppression after a course of bioflavonoid treatment. Suspension of the bioflafonoid complex was introduced to the male mice (СВАхC57Bl/6)F1 aged 12- 14 weeks at a daily dose of 2 mg/animal (80 mg/kg), per os, using gastric catheter, over 14 days. Cytostatic immunosuppression was produced by a single intraperitoneal Cy injection. Proliferative activity of spleen and thymic cells was determined by standard method with Н3 -thymidine incorporation in the 72-h cell culture. Cellular immune response was assayed by the degree of delayed-type hypersensitivity development in response to sheep erythrocytes. The number of hematopoietic progenitors was evaluated by culturing bone marrow cells in methylcellulose-based medium. The experiments have shown mitigation of immunosuppressive effects induced by Cy, in the course of bioflavonoid complex treatment, with respect to absolute and relative mass of lymphoid organs and leukocyte numbers in peripheral blood. Moreover, we have demonstrated decreased effects of Cy treatment upon the spontaneous activity of spleen cells, mitogen-induced thymocyte and splenocyte proliferation, intensivity of delayed-type hypersensitivity response that reached the values of intact animals. Following the course of bioflavonoids, we have revealed an increase in early hematopoietic progenitors. Alleviation of Cy-induced suppressive effects upon cellular immune response, proliferation rates of immune cells, as well as stimulation of hematopoietic stem cell functions suggest a sufficient capacity of the original bioflavonoid complex for modulation of immunity and hematopoiesis, thus presenting experimental proofs for its potential usage as an adjuvant treatment of the patients with malignant diseases.

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