scholarly journals CD4+ Th immunogenicity of the Ascaris spp. secreted products

2019 ◽  
Author(s):  
Friederike Ebner ◽  
Eliot Morrison ◽  
Miriam Bertazzon ◽  
Ankur Midha ◽  
Susanne Hartmann ◽  
...  

SummaryAscaris spp. is a major health problem of humans and animals alike, and understanding the immunogenicity of its antigens is required for developing urgently needed vaccines. The parasite-secreted products represent the most relevant, yet highly complex (>250 proteins) antigens of Ascaris spp. as defining the pathogen-host interplay. We applied an in vitro antigen processing system coupled to quantitative proteomics to identify potential CD4+ Th cell epitopes in Ascaris suum-secreted products. This approach restricts the theoretical list of epitopes, based on affinity prediction, by a factor of ∼1200. More importantly, selection of 2 candidate peptides based on experimental evidence demonstrated the presence of epitope-reactive T cells in Ascaris-specific T cell lines generated from healthy human individuals. Thus, this stringent work pipeline identifies a human haplotype-specific T cell epitope of a major human pathogen. The methodology described represents an easily adaptable platform for characterization of highly complex pathogenic antigens and their MHCII-restriction.

2002 ◽  
Vol 70 (1) ◽  
pp. 79-85 ◽  
Author(s):  
Maddalena Panigada ◽  
Tiziana Sturniolo ◽  
Giorgio Besozzi ◽  
Maria Giovanna Boccieri ◽  
Francesco Sinigaglia ◽  
...  

ABSTRACT The characterization of Mycobacterium tuberculosis antigens inducing CD4+ T-cell responses could critically contribute to the development of subunit vaccines for M. tuberculosis. Here we performed computational analysis by using T-cell epitope prediction software (known as TEPITOPE) to predict promiscuous HLA-DR ligands in the products of the mce genes of M. tuberculosis. The analysis of the proliferative responses of CD4+ T cells from patients with pulmonary tuberculosis to selected peptides displaying promiscuous binding to HLA-DR in vitro led us to the identification of a peptide that induced proliferation of CD4+ cells from 50% of the tested subjects. This study demonstrates that a systematic computational approach can be used to identify T-cell epitopes in proteins expressed by an intracellular pathogen.


2020 ◽  
Vol 7 (9) ◽  
pp. 201141 ◽  
Author(s):  
Seema Mishra

Novel coronavirus, SARS-CoV-2, has emerged as one of the deadliest pathogens of this century, creating an unprecedented pandemic. Belonging to the betacoronavirus family, it primarily spreads through human contact via symptomatic and asymptomatic transmission. Despite several attempts since it emerged, there is no known treatment in the form of drugs or vaccines. Hence, work on developing a potential multi-subunit vaccine is the need of the hour. In this study, attempts have been made to find globally conserved epitopes from the entire set of SARS-CoV-2 proteins as there is as yet, no clear information on the immunogenicity of these proteins. Using diverse computational tools, a ranked list of probable immunogenic, promiscuous epitopes generated through all the three main stages of antigen processing and presentation pathways has been prioritized. Moreover, several useful insights were gleaned during these analyses. One of the most important insights is that all of the proteins in this pathogen present unique epitopes, so that the targeting of a few specific viral proteins is not likely to result in an effective immune response in humans. Due to the presence of these unique epitopes in all of the SARS-CoV-2 proteins, stronger immune responses generated by T cell hyperactivation may lead to cytokine storm and immunopathology and consequently, remote chances of human survival. These epitopes, after due validation in vitro , may thus need to be presented to the human body in that form of multi-subunit epitope-based vaccine that avoids such immunopathologies.


Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 429-435
Author(s):  
E Boven ◽  
T Lindmo ◽  
JB Mitchell ◽  
PA Jr Bunn

The radiolabeled anti-T cell antibody T101 can be used for specific tumor localization, but unlabeled T101 produces limited cytotoxicity in patients. We thus studied the in vitro cytotoxic effects of T101 labeled with 125I, a radionuclide known for its short-range, high- linear-energy electrons. We showed that 125I-T101 could be readily prepared at high specific activity with high immunoreactivity. Human malignant T cell lines HUT 102, MOLT-4, and HUT 78 were found to differ in the number of T65 determinants (the antigen recognized by T101) and the sensitivity to external x-ray radiation, which were of significance for the cytotoxicity of 125I-T101 in vitro. The cytotoxic effects of 125I-T101 were also found to be dose dependent and increased with exposure time under frozen conditions. As controls, unlabeled T101 had no cytotoxic effect, while free Na 125I or the 125I-labeled irrelevant antibody 9.2.27 exerted minor cytotoxicity. In HUT 102 and MOLT-4, more than 3 logs' cell killing was achieved within four weeks. Because considerable cytotoxicity was demonstrated in vitro by 125I-T101 on T65- positive malignant cells, and because low-dose 111In-T101 can be used successfully for tumor localization, future trials using 125I-T101 at high specific radioactivity may improve therapeutic results in patients with T65-positive malignancies.


2018 ◽  
Vol 12 (2) ◽  
pp. 66-72
Author(s):  
Ban Hussein Ali ◽  
Thaer A. Saleh ◽  
Mohammed M. Al-Halbosiy

            Leishmaniasis is a widespread parasitic disease caused by Leishmania parasite, this disease considers as a major health problem worldwide. The available therapy is unsatisfactory expensive with a cytotoxic side effects. Studies of marine algae as a source of pharmacological active compounds have increased worldwide.  This study was aimed to investigate the effect of a type of green algae (Chara vulgaris) on promastigotes of L. tropica, by using. various concentrations (500, 250, 125, 62.5, 31.25, 15.6 µg/mL) in vitro by MTT assay [3-(4.5-dimethylthiazol-2-yl)- 2.5-diphenyl tetrazolium bromide)], to investigate its effect on the proliferation of promastigotes, by three incubation periods (24, 48, 72 hr.) The results showed a significant (p< 0.05)   decrease in survived of promastigotes in treatment groups with concentrations that ranged between 15 to 500 μg/ ml.  This study revealed a major growth inhibition effect of the organic extract of C. vulgaris against L. tropica promastigotes, and the extract of ethyl acetate showed potential activity is better than the aqueous extract.


2019 ◽  
Author(s):  
Guangzhi Wang ◽  
Huihui Wan ◽  
Xingxing Jian ◽  
Yuyu Li ◽  
Jian Ouyang ◽  
...  

AbstractIn silico T-cell epitope prediction plays an important role in immunization experimental design and vaccine preparation. Currently, most epitope prediction research focuses on peptide processing and presentation, e.g. proteasomal cleavage, transporter associated with antigen processing (TAP) and major histocompatibility complex (MHC) combination. To date, however, the mechanism for immunogenicity of epitopes remains unclear. It is generally agreed upon that T-cell immunogenicity may be influenced by the foreignness, accessibility, molecular weight, molecular structure, molecular conformation, chemical properties and physical properties of target peptides to different degrees. In this work, we tried to combine these factors. Firstly, we collected significant experimental HLA-I T-cell immunogenic peptide data, as well as the potential immunogenic amino acid properties. Several characteristics were extracted, including amino acid physicochemical property of epitope sequence, peptide entropy, eluted ligand likelihood percentile rank (EL rank(%)) score and frequency score for immunogenic peptide. Subsequently, a random forest classifier for T cell immunogenic HLA-I presenting antigen epitopes and neoantigens was constructed. The classification results for the antigen epitopes outperformed the previous research (the optimal AUC=0.81, external validation data set AUC=0.77). As mutational epitopes generated by the coding region contain only the alterations of one or two amino acids, we assume that these characteristics might also be applied to the classification of the endogenic mutational neoepitopes also called ‘neoantigens’. Based on mutation information and sequence related amino acid characteristics, a prediction model of neoantigen was established as well (the optimal AUC=0.78). Further, an easy-to-use web-based tool ‘INeo-Epp’ was developed (available at http://www.biostatistics.online/INeo-Epp/neoantigen.php)for the prediction of human immunogenic antigen epitopes and neoantigen epitopes.


2010 ◽  
Vol 33 (6) ◽  
pp. e75-e80 ◽  
Author(s):  
Yang Xiao-meng ◽  
Jiang Li-fang ◽  
Tang Yun-xia ◽  
Yin Yue ◽  
Liu Wen-quan ◽  
...  

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