scholarly journals Evaluation of Two Homologous Proline-Rich Proteins of Coccidioides posadasii as Candidate Vaccines against Coccidioidomycosis

2007 ◽  
Vol 75 (12) ◽  
pp. 5777-5787 ◽  
Author(s):  
Roger A. Herr ◽  
Chiung-Yu Hung ◽  
Garry T. Cole
Keyword(s):  
T Cell ◽  
Pulmonary Infection ◽  
Vaccine Candidate ◽  
Protective Efficacy ◽  
T Cell Epitopes ◽  
T Cell Repertoire ◽  
Coccidioides Posadasii ◽  
Cell Repertoire ◽  
Protein Sequence Identity ◽  
Combined Vaccine

ABSTRACT Evaluation of the protective efficacy of recombinant T-cell-reactive proteins of Coccidioides posadasii in a murine model of coccidioidomycosis has led to the discovery of potential vaccines against this respiratory disease. A recombinant proline-rich antigen (rAg2/Pra) has been reported to be a leading vaccine candidate. However, contradictory results exist on the protection afforded by this antigen. Subcutaneous vaccination of either C57BL/6 or BALB/c mice with rAg2/Pra plus adjuvant followed by intraperitoneal challenge with C. posadasii resulted in a significant reduction of the fungal burden at 12 to 14 days postchallenge compared to that in nonvaccinated animals. Use of the same vaccination protocol followed by intranasal (i.n.) challenge of C57BL/6 mice with an equal number of organisms culminated in chronic pulmonary infection or death over a 90-day period. Early studies of Ag2/Pra suggested that it is a component of an immunogenic complex. We reveal in this study that C. posadasii produces a homolog of the reported proline-rich antigen, designated Prp2, which shows 69% protein sequence identity and 86% similarity to Ag2/Pra. Protection against i.n. challenge of C57BL/6 mice was evaluated by vaccination with the single bacterially expressed homolog, rAg2/Pra, or rPrp2 in combination with rAg2/Pra, each in the presence of the same adjuvant. The combined vaccine provided significantly better protection than either of the single recombinant protein vaccines. Results of enzyme-linked immunospot assays of the immunized mice revealed that the two proline-rich homologs contain unique T-cell epitopes. In combination, the recombinant proteins stimulate a more heterogeneous and protective T-cell repertoire than the monovalent vaccines.

Major contribution of codominant CD8 and CD4 T cell epitopes to the human cytomegalovirus-specific T cell repertoire

2005 ◽  
Vol 62 (1) ◽  
pp. 77-86 ◽  
Author(s):  
M. -D. Nastke† ◽  
L. Herrgen† ◽  
S. Walter ◽  
D. Wernet ◽  
H. -G. Rammensee ◽  
...  
Keyword(s):  
T Cell ◽  
Human Cytomegalovirus ◽  
Cd4 T Cell ◽  
T Cell Epitopes ◽  
T Cell Repertoire ◽  
Cell Repertoire

scholarly journals A Recombinant Aspartyl Protease of Coccidioides posadasii Induces Protection against Pulmonary Coccidioidomycosis in Mice

2006 ◽  
Vol 74 (1) ◽  
pp. 516-527 ◽  
Author(s):  
Eric J. Tarcha ◽  
Venkatesha Basrur ◽  
Chiung-Yu Hung ◽  
Malcolm J. Gardner ◽  
Garry T. Cole
Keyword(s):  
T Cells ◽  
T Cell ◽  
Fungal Pathogens ◽  
Pulmonary Infection ◽  
Polyacrylamide Gel Electrophoresis ◽  
Experimental Studies ◽  
T Cell Epitopes ◽  
Coccidioides Posadasii ◽  
Human Major Histocompatibility Complex

ABSTRACT Coccidioidomycosis is a respiratory disease of humans caused by the desert soil-borne fungal pathogens Coccidioides spp. Recurrent epidemics of this mycosis in the southwestern United States have contributed significantly to escalated health care costs. Clinical and experimental studies indicate that prior symptomatic coccidioidomycosis induces immunity against subsequent infection, and activation of T cells is essential for containment of the pathogen and its clearance from host tissue. Development of a human vaccine against coccidioidomycosis has focused on recombinant T-cell-reactive antigens which elicit a durable protective immune response against pulmonary infection in mice. In this study we fractionated a protective multicomponent parasitic cell wall extract in an attempt to identify T-cell antigens. Immunoblots of electrophoretic separations of this extract identified patient seroreactive proteins which were subsequently excised from two-dimensional polyacrylamide gel electrophoresis gels, trypsin digested, and sequenced by tandem mass spectrometry. The full-length gene which encodes a dominant protein in the immunoblot was identified using established methods of bioinformatics. The gene was cloned and expressed, and the recombinant protein was shown to stimulate immune T cells in vitro. The deduced protein was predicted to contain epitopes that bind to human major histocompatibility complex class II molecules using a TEPITOPE-based algorithm. Synthetic peptides corresponding to the predicted T-cell epitopes induced gamma interferon production by immune T lymphocytes. The T-cell-reactive antigen, which is homologous to secreted fungal aspartyl proteases, protected mice against pulmonary infection with Coccidioides posadasii. We argue that this immunoproteomic/bioinformatic approach to the identification of candidate vaccines against coccidioidomycosis is both efficient and productive.

scholarly journals Drug and Chemical Allergy: A Role for a Specific Naive T-Cell Repertoire?

2021 ◽  
Vol 12 ◽  
Author(s):  
Rami Bechara ◽  
Alexia Feray ◽  
Marc Pallardy
Keyword(s):  
T Cells ◽  
T Cell ◽  
Rare Event ◽  
Thymic Selection ◽  
T Cell Epitopes ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Naïve T Cell ◽  
Naive T Cell ◽  
Selection Of

Allergic reactions to drugs and chemicals are mediated by an adaptive immune response involving specific T cells. During thymic selection, T cells that have not yet encountered their cognate antigen are considered naive T cells. Due to the artificial nature of drug/chemical-T-cell epitopes, it is not clear whether thymic selection of drug/chemical-specific T cells is a common phenomenon or remains limited to few donors or simply does not exist, suggesting T-cell receptor (TCR) cross-reactivity with other antigens. Selection of drug/chemical-specific T cells could be a relatively rare event accounting for the low occurrence of drug allergy. On the other hand, a large T-cell repertoire found in multiple donors would underline the potential of a drug/chemical to be recognized by many donors. Recent observations raise the hypothesis that not only the drug/chemical, but also parts of the haptenated protein or peptides may constitute the important structural determinants for antigen recognition by the TCR. These observations may also suggest that in the case of drug/chemical allergy, the T-cell repertoire results from particular properties of certain TCR to recognize hapten-modified peptides without need for previous thymic selection. The aim of this review is to address the existence and the role of a naive T-cell repertoire in drug and chemical allergy. Understanding this role has the potential to reveal efficient strategies not only for allergy diagnosis but also for prediction of the immunogenic potential of new chemicals.

Comprehensive analysis of melanoma antigen specific T cell repertoire: EPIMAX (EPItope MAXimum)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3016-3016
Author(s):  
A. Palucka ◽  
J. Banchereau ◽  
L. Vence ◽  
J. Connolly ◽  
J. Fay ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Tumor Cells ◽  
Cd4 T Cells ◽  
T Cell Epitopes ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Melanoma Antigen ◽  
Allogeneic Tumor

3016 Background: We have demonstrated in phase I clinical trial treating 20 patients with metastatic melanoma that dendritic cells (DCs) loaded with killed allogeneic tumor cells can elicit immune and clinical responses. Loading DC vaccines with killed allogeneic tumor cells allows: i) presentation of antigens via both MHC class I and class II, ii) strong help, iii) applicability to any cancer, and iv) loading tumor antigen independent of HLA haplotype of the patient. However, this renders the immunomonitoring step complex as the antigens and their restriction elements are unknown. To address this issue, we developed EPIMAX. Methods: EPIMAX measures simultaneously cell proliferation and secretion of multiple cytokines that distinguish Type 1, Type 2 cytokines and IL-10 secretion using Luminex. Briefly, 5x105 CFSE-labeled PBMCs are plated with peptide pools of overlapping peptide libraries from appropriate antigens. After 48hrs, supernatants are transferred for cytokine determination. After an additional 6 days of culture, cell proliferation is analyzed by flow cytometry after staining for surface markers CD4 and CD8. Results: We demonstrated that EPIMAX permits us to assess: i) Specificity and breadth of induced immune responses, ii) Type of induced immunity (Type I, Type II, IL-10), and iii) Function of specific T cells as measured by cytokine secretion and proliferation. To date 8 patients with stage IV melanoma were analyzed at baseline and after vaccination with DCs loaded with killed allogeneic melanoma cells. We assessed epitopes derived from MART-1, NY-ESO1, TRP-1 and gp100. Analysis of CD8+T cells: We have identified 15 melanoma antigen CD8+T cell epitopes in 8 patients. These include: three Tc0 epitopes (IL2), and twelve Tc1 epitopes triggering IP-10 secretion. Analysis of CD4+T cells: We have identified 15 melanoma antigen CD4+T cell epitopes in 5 patients. These include: nine Th0 epitopes (IL2), four Th1 epitopes (IFNγ) and two Th2 epitopes (IL13). Finally, we analyzed secretion of IL-10 and found thus far IL-10 secreting CD4+T cells in seven patients. Further studies demonstrated that these T cells have regulatory function. Conclusions: EPIMAX permits comprehensive assessment of melanoma antigen specific T cell repertoire. No significant financial relationships to disclose.

Peripheral T-cell repertoire alterations are common and affect outcome in large cell neuroendocrine lung carcinoma

Pneumologie ◽  
2018 ◽  
Vol 72 (S 01) ◽  
pp. S53-S54
Author(s):  
P Christopoulos ◽  
M Schneider ◽  
F Bozorgmehr ◽  
W Engel-Riedel ◽  
C Kropf-Sanchen ◽  
...  
Keyword(s):  
T Cell ◽  
Lung Carcinoma ◽  
Large Cell ◽  
T Cell Repertoire ◽  
Cell Repertoire
Sign in / Sign up

Export Citation Format

Share Document