Genetic Composition and Evolution of the Prevalent Mycobacterium Tuberculosis Lineages 2 and 4 in the Chinese and Zhejiang Province Populations

Abstract Background: There are seven human-adaptation lineages of Mycobacterium tuberculosis (Mtb). Tuberculosis (TB) dissemination is strongly influenced by human movements and host genetics. The detailed lineage distribution evolution of Mtb in Zhejiang Province is unknown. We aim to determine how different sub-lineages are transmitted and distributed within China and Zhejiang Province.Methods: We analyzed whole-genome sequencing data for a countrywide collection of 1154 isolates and a provincial collection of 1296 isolates, constructed the best-scoring maximum likelihood phylogenetic tree. Bayesian evolutionary analysis was used to calculate the latest common ancestor of lineages 2 and 4. The antigenic diversity of human T cell epitopes was evaluated by calculating the pairwise dN/dS ratios.Results: Of the Zhejiang isolates, 964 (74.38%) belonged to lineage 2 and 332 (25.62%) belonged to lineage 4. The distributions of the sub-lineages varied across the geographic regions of Zhejiang Province. L2.2 is the most ancient sub-lineage in Zhejiang, first appearing approximately 6897 years ago (95% HDI: 6513-7298). L4.4 is the most modern sub-lineage, first appearing approximately 2217 years ago (95% HDI: 1864-2581). The dN/dS ratios showed that the epitope and non-epitope regions of lineage 2 strains were significantly (P<0.001) more conserved than those of lineage 4.Conclusions: An increase in the frequency of lineage 4 may reflect its successful transmission over the last 20 years. The recent common ancestors of the sub-lineages and their transmission routes are relevant to the entry of humans into China and Zhejiang Province. Diversity in T cell epitopes may prevent Mycobacterium tuberculosis from being recognized by the immune system.

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Genetic composition and evolution of the prevalent Mycobacterium tuberculosis lineages 2 and 4 in the Chinese and Zhejiang Province populations

Cell & Bioscience ◽

10.1186/s13578-021-00673-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Beibei Wu ◽

Wenlong Zhu ◽

Yue Wang ◽

Qi Wang ◽

Lin Zhou ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

T Cell ◽

Zhejiang Province ◽

Whole Genome Sequencing Data ◽

Evolutionary Analysis ◽

T Cell Epitopes ◽

Sequencing Data ◽

Human T Cell ◽

Lineage 2 ◽

Highest Posterior Density

Abstract Background There are seven human-adaptation lineages of Mycobacterium tuberculosis (Mtb). Tuberculosis (TB) dissemination is strongly influenced by human movements and host genetics. The detailed lineage distribution evolution of Mtb in Zhejiang Province is unknown. We aim to determine how different sub-lineages are transmitted and distributed within China and Zhejiang Province. Methods We analysed whole-genome sequencing data for a worldwide collection of 1154 isolates and a provincial collection of 1296 isolates, constructed the best-scoring maximum likelihood phylogenetic tree. Bayesian evolutionary analysis was used to calculate the latest common ancestor of lineages 2 and 4. The antigenic diversity of human T cell epitopes was evaluated by calculating the pairwise dN/dS ratios. Results Of the Zhejiang isolates, 964 (74.38%) belonged to lineage 2 and 332 (25.62%) belonged to lineage 4. The distributions of the sub-lineages varied across the geographic regions of Zhejiang Province. L2.2 is the most ancient sub-lineage in Zhejiang, first appearing approximately 6897 years ago (95% highest posterior density interval (HDI): 6513–7298). L4.4 is the most modern sub-lineage, first appearing approximately 2217 years ago (95% HDI: 1864–2581). The dN/dS ratios showed that the epitope and non-epitope regions of lineage 2 strains were significantly (P < 0.001) more conserved than those of lineage 4. Conclusions An increase in the frequency of lineage 4 may reflect its successful transmission over the last 20 years. The recent common ancestors of the sub-lineages and their transmission routes are relevant to the entry of humans into China and Zhejiang Province. Diversity in T cell epitopes may prevent Mycobacterium tuberculosis from being recognized by the immune system.

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Genetic composition and evolution of the prevalent Mycobacterium tuberculosis lineages 2 and 4 in the Chinese and Zhejiang Province populations

10.1101/2020.11.07.372573 ◽

2020 ◽

Author(s):

Beibei Wu ◽

Wenlong Zhu ◽

Yue Wang ◽

Qi Wang ◽

Lin Zhou ◽

...

Keyword(s):

Zhejiang Province ◽

Whole Genome Sequencing Data ◽

Evolutionary Analysis ◽

T Cell Epitopes ◽

Sequencing Data ◽

Maximum Likelihood Phylogenetic Tree ◽

Human T Cell ◽

Human Movements ◽

Lineage 2 ◽

Common Ancestors

AbstractThe causative agent of tuberculosis (TB) comprises seven human-adapted lineages. Human movements and host genetics are crucial to TB dissemination. We analyzed whole-genome sequencing data for a countrywide collection of 1154 isolates and a provincial collection of 1296 isolates, constructed the best-scoring maximum likelihood phylogenetic tree, conducted Bayesian evolutionary analysis to compute the most recent common ancestors of lineages 2 and 4, and assessed the antigenic diversity in human T cell epitopes by calculating pairwise dN/dS ratios. Of the 1296 Zhejiang isolates, 964 (74.38%) belonged to lineage 2 and 332 (25.62%) belonged to lineage 4. L2.2 is the most ancient sub-lineage in Zhejiang, first appearing approximately 6897 years ago (95% HDI: 6513-7298). L4.4 is the most modern sub-lineage, first appearing approximately 2217 years ago (95% HDI: 1864-2581). The dN/dS ratios revealed that the epitope and non-epitope regions of lineage 2 strains were significantly (P<0.001) more conserved than those of lineage 4. An increase in the frequency of lineage 4 may reflect its successful transmission over the last 20 years. The recent common ancestors and transmission routes of the sub-lineages are related to the entry of humans into China and Zhejiang Province.

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Identification of T-cell epitopes on E2 protein of rubella virus, as recognized by human T-cell lines and clones.

Journal of Virology ◽

10.1128/jvi.66.11.6788-6793.1992 ◽

1992 ◽

Vol 66 (11) ◽

pp. 6788-6793 ◽

Cited By ~ 13

Author(s):

D Ou ◽

P Chong ◽

Y Choi ◽

P McVeigh ◽

W A Jefferies ◽

...

Keyword(s):

T Cell ◽

Cell Lines ◽

Rubella Virus ◽

T Cell Epitopes ◽

E2 Protein ◽

Human T Cell ◽

T Cell Lines

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SARS-CoV-2 Human T cell Epitopes: adaptive immune response against COVID-19.

Cell Host & Microbe ◽

10.1016/j.chom.2021.05.010 ◽

2021 ◽

Author(s):

Alba Grifoni ◽

John Sidney ◽

Randi Vita ◽

Bjoern Peters ◽

Shane Crotty ◽

...

Keyword(s):

Immune Response ◽

T Cell ◽

Adaptive Immune Response ◽

T Cell Epitopes ◽

Adaptive Immune ◽

Human T Cell

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Human T cell receptor occurrence patterns encode immune history, genetic background, and receptor specificity

eLife ◽

10.7554/elife.38358 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 42

Author(s):

William S DeWitt ◽

Anajane Smith ◽

Gary Schoch ◽

John A Hansen ◽

Frederick A Matsen ◽

...

Keyword(s):

T Cell ◽

T Cell Receptor ◽

Genetic Background ◽

Cell Receptor ◽

Sequencing Data ◽

Human T Cell ◽

Disease Associations ◽

Repertoire Sequencing ◽

Mhc Polymorphism ◽

Occurrence Patterns

The T cell receptor (TCR) repertoire encodes immune exposure history through the dynamic formation of immunological memory. Statistical analysis of repertoire sequencing data has the potential to decode disease associations from large cohorts with measured phenotypes. However, the repertoire perturbation induced by a given immunological challenge is conditioned on genetic background via major histocompatibility complex (MHC) polymorphism. We explore associations between MHC alleles, immune exposures, and shared TCRs in a large human cohort. Using a previously published repertoire sequencing dataset augmented with high-resolution MHC genotyping, our analysis reveals rich structure: striking imprints of common pathogens, clusters of co-occurring TCRs that may represent markers of shared immune exposures, and substantial variations in TCR-MHC association strength across MHC loci. Guided by atomic contacts in solved TCR:peptide-MHC structures, we identify sequence covariation between TCR and MHC. These insights and our analysis framework lay the groundwork for further explorations into TCR diversity.

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Sequence Diversity in the pe_pgrs Genes of Mycobacterium tuberculosis Is Independent of Human T Cell Recognition

mBio ◽

10.1128/mbio.00960-13 ◽

2014 ◽

Vol 5 (1) ◽

Cited By ~ 60

Author(s):

Richard Copin ◽

Mireia Coscollá ◽

Salome N. Seiffert ◽

Graham Bothamley ◽

Jayne Sutherland ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

T Cell ◽

Sequence Variation ◽

Large Family ◽

Sequence Diversity ◽

Cell Recognition ◽

T Cell Epitopes ◽

Content Type ◽

T Cell Recognition ◽

Human T Cell

ABSTRACTTheMycobacterium tuberculosisgenome includes the large family ofpe_pgrsgenes, whose functions are unknown. Because of precedents in other pathogens in which gene families showing high sequence variation are involved in antigenic variation, a similar role has been proposed for thepe_pgrsgenes. However, the impact of immune selection onpe_pgrsgenes has not been examined. Here, we sequenced 27pe_pgrsgenes in 94 clinical strains from five phylogenetic lineages of theM. tuberculosiscomplex (MTBC). We found thatpe_pgrsgenes were overall more diverse than the remainder of the MTBC genome, but individual members of the family varied widely in their nucleotide diversity and insertion/deletion (indel) content: some were more, and others were much less, diverse than the genome average. Individualpe_pgrsgenes also differed in the ratio of nonsynonymous to synonymous mutations, suggesting that different selection pressures act on individualpe_pgrsgenes. Using bioinformatic methods, we tested whether sequence diversity inpe_pgrsgenes might be selected by human T cell recognition, the major mechanism of adaptive immunity to MTBC. We found that the large majority of predicted human T cell epitopes were confined to the conserved PE domain and experimentally confirmed the antigenicity of this domain in tuberculosis patients. In contrast, despite being genetically diverse, the PGRS domains harbored few predicted T cell epitopes. These results indicate that human T cell recognition is not a significant force driving sequence diversity inpe_pgrsgenes, which is consistent with the previously reported conservation of human T cell epitopes in the MTBC.IMPORTANCERecognition ofMycobacterium tuberculosisantigens by T lymphocytes is known to be important for immune protection against tuberculosis, but it is unclear whether human T cell recognition drives antigenic variation inM. tuberculosis. We previously discovered that the known human T cell epitopes in theM. tuberculosiscomplex are highly conserved, but we hypothesized that undiscovered epitopes with naturally occurring sequence variants might exist. To test this hypothesis, we examined thepe_pgrsgenes, a large family of genes that has been proposed to function in immune evasion byM. tuberculosis. We found that thepe_pgrsgenes exhibit considerable sequence variation, but the regions containing T cell epitopes and the regions of variation are distinct. These findings confirm that the majority of human T cell epitopes ofM. tuberculosisare highly conserved and indicate that selection forces other than T cell recognition drive sequence variation in thepe_pgrsgenes.

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