Dataset Information

Identification of the Ligands of TCR?? by Screening the Immune Repertoire of ??T Cells From Patients With Tuberculosis.

ABSTRACT: Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection is a serious threat to human health. ??T cells, which are characterized by major histocompatibility complex (MHC) non-restriction, are rapidly activated and initiate anti-infectious immune responses in the early stages of Mtb infection. However, the mechanism underlying the recognition of Mtb by ??T cells remains unclear. In this study, we characterized the pattern of the human T-cell receptor (TCR) ?? complementary determinant region 3 (CDR3) repertoire in TB patients by using high-throughput immune repertoire sequencing. The results showed that the diversity of CDR3? was significantly reduced and that the frequency of different gene fragments (V/J), particularly the V-segment of the ?-chain, was substantially altered, which indicate that TB infection-related ??T cells, especially the ? genes, were activated and amplified in TB patients. Then, we screened the Mtb-associated epitopes/proteins recognized by ??T cells using an Mtb proteome chip with dominant CDR3? peptides as probes. We identified the Mtb protein Rv0002 as a potential ligand capable of stimulating the activation and proliferation of ??T cells. Our findings provide a further understanding of the mechanisms underlying ??T cell-mediated immunity against Mtb infection.

SUBMITTER: Li Y

PROVIDER: S-EPMC6769167 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Identification of the Ligands of TCRγδ by Screening the Immune Repertoire of γδT Cells From Patients With Tuberculosis.

Li Yuxia Y Wang Xinfeng X Teng Da D Chen Hui H Wang Maoshui M Wang Junling J Zhang Jianmin J He Wei W

Frontiers in immunology 20190924

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection is a serious threat to human health. γδT cells, which are characterized by major histocompatibility complex (MHC) non-restriction, are rapidly activated and initiate anti-infectious immune responses in the early stages of Mtb infection. However, the mechanism underlying the recognition of Mtb by γδT cells remains unclear. In this study, we characterized the pattern of the human T-cell receptor (TCR ...[more]

PMID: 31608066

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Project description:Objective To study the tissue-infiltrating immune cells of the emphysema phenotype of chronic obstructive pulmonary disease (COPD) and find the molecular mechanism related to the development of emphysema to offer potential targets for more precise treatment of patients with COPD. Methods Combined analyses of COPD emphysema phenotype lung tissue-related datasets, GSE47460 and GSE1122, were performed. CIBERSORT was used to assess the distribution of tissue-infiltrating immune cells. Weighted gene co-expression network analysis (WGCNA) was used to select immune key genes closely related to clinical features. Rt-qPCR experiments were used for the validation of key genes. Emphysema risk prediction models were constructed by logistic regression analysis and a nomogram was developed. Results In this study, three immune cells significantly associated with clinical features of emphysema (FEV1 post-bronchodilator % predicted, GOLD Stage, and DLCO) were found. The proportion of neutrophils (p=0.025) infiltrating in the emphysema phenotype was significantly increased compared with the non-emphysema phenotype, while the proportions of M2 macrophages (p=0.004) and resting mast cells (p=0.01) were significantly decreased. Five immune-related differentially expressed genes (DEGs) were found. WGCNA and clinical lung tissue validation of patients with emphysema phenotype were performed to further screen immune-related genes closely related to clinical features. A key gene (SERPINA3) was selected and included in the emphysema risk prediction model. Compared with the traditional clinical prediction model (AUC=0.923), the combined prediction model, including SERPINA3 and resting mast cells (AUC=0.941), had better discrimination power and higher net benefit. Conclusion This study comprehensively analyzed the tissue-infiltrating immune cells significantly associated with emphysema phenotype, including M2 macrophages, neutrophils, and resting mast cells, and identified SERPINA3 as a key immune-related gene.

Project description:BackgroundStudying the potential etiology and pathogenesis of tuberculosis-associated chronic obstructive pulmonary disease (TOPD) from an autoimmunity perspective may provide insights into peripheral blood autoantibodies and immune cells, as well as their interactions.MethodsThis study examined the serum autoantibody repertoire in healthy individuals, patients with chronic obstructive pulmonary disease (COPD), patients with pulmonary tuberculosis (TB), and TOPD patients using the HuProtTM protein chip. Autoantigens in the peripheral blood of TOPD patients were verified using ELISA assay. Various epitopes and immune simulation were predicted using bioinformatic methods. Flow cytometry was employed to detect macrophages(Mφ), T cells, and innate lymphoid cells (ILCs) in the peripheral blood.ResultsCOPD patients displayed distinct alterations in their IgG and IgM autoantibodies compared to the other groups. GeneOntology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses revealed that these autoantibodies were associated with regulating macrophages, T cells, and B cells. ELISA results confirmed the upregulation of expression of proliferating cell nuclear antigen (PCNA), Mitogen-Activated Protein Kinase 3 antigen (MAPK3), and threonine protein kinase 1 antigen (AKT1) proteins in the peripheral blood of TOPD patients. Bioinformatic analysis predicted multiple potential epitopes in Th, CTL, and B cells. Immune simulation results demonstrated that PCNA, MAPK3, and AKT1 can activate innate and adaptive immune responses and induce the expression of different cytokines, such as IFN-g and IL-2. Furthermore, data obtained from flow cytometry assay revealed an upregulation in the face of Th1 cells in the peripheral blood of TOPD patients.ConclusionTuberculosis infection can effectively induce autoimmune responses, contributing to increased expression of Th1 cells and associated cytokines, ultimately leading to immune dysregulation. Furthermore, the accumulation of pulmonary inflammatory response facilitates the progression of TOPD and is helpful for the clinical diagnosis and the development of targeted therapeutic drugs for this disease.

Project description:BackgroundThe importance of CD4⁺ and CD8⁺ T cells in protection against tuberculosis (TB) is well known, however, the association between changes to the T cell repertoire and disease presentation has never been analyzed. Characterization of T-cells in TB patients in previous study only analyzed the TCR β chain and omitted analysis of the Vα family even though α chain also contribute to antigen recognition. Furthermore, limited information is available regarding the heterogeneity compartment and overall function of the T cells in TB patients as well as the common TCR structural features of Mtb antigen specific T cells among the vast numbers of TB patients.Methodology/principal findingsCDR3 spectratypes of CD4⁺ and CD8⁺ T cells were analyzed from 86 patients with TB exhibiting differing degrees of disease severity, and CDR3 spectratype complexity scoring system was used to characterize TCR repertoire diversity. TB patients with history of other chronic disease and other bacterial or viral infections were excluded for the study to decrease the likely contribution of TCRs specific to non-TB antigens as far as possible. Each patient was age-matched with a healthy donor group to control for age variability. Results showed that healthy controls had a normally diversified TCR repertoire while TB patients represented with restricted TCR repertoire. Patients with mild disease had the highest diversity of TCR repertoire while severely infected patients had the lowest, which suggest TCR repertoire diversity inversely correlates with disease severity. In addition, TB patients showed preferred usage of certain TCR types and have a bias in the usage of variable (V) and joining (J) gene segments and N nucleotide insertions.Conclusions/significanceResults from this study promote a better knowledge about the public characteristics of T cells among TB patients and provides new insight into the TCR repertoire associated with clinic presentation in TB patients.

Dataset Information

Identification of the Ligands of TCR?? by Screening the Immune Repertoire of ??T Cells From Patients With Tuberculosis.

Publications

Identification of the Ligands of TCRγδ by Screening the Immune Repertoire of γδT Cells From Patients With Tuberculosis.

Similar Datasets

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