T Cell Receptor Repertoire Analysis Reveals Signatures of T Cell Responses to Human Mycobacterium tuberculosis
Characterization of T cell receptor (TCR) repertoires is essential for understanding the mechanisms of Mycobacterium tuberculosis (Mtb) infection involving T cell adaptive immunity. The characteristics of TCR sequences and distinctive signatures of T cell subsets in tuberculous patients are still un...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.829694/full |
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| author | Ming-Ming Shao Feng-Shuang Yi Zhong-Yin Huang Peng Peng Feng-Yao Wu Huan-Zhong Shi Kan Zhai |
| author_facet | Ming-Ming Shao Feng-Shuang Yi Zhong-Yin Huang Peng Peng Feng-Yao Wu Huan-Zhong Shi Kan Zhai |
| author_sort | Ming-Ming Shao |
| collection | DOAJ |
| description | Characterization of T cell receptor (TCR) repertoires is essential for understanding the mechanisms of Mycobacterium tuberculosis (Mtb) infection involving T cell adaptive immunity. The characteristics of TCR sequences and distinctive signatures of T cell subsets in tuberculous patients are still unclear. By combining single-cell TCR sequencing (sc-TCR seq) with single-cell RNA sequencing (sc-RNA seq) and flow cytometry to characterize T cells in tuberculous pleural effusions (TPEs), we identified 41,718 CD3+ T cells in TPEs and paired blood samples, including 30,515 CD4+ T cells and 11,203 CD8+ T cells. Compared with controls, no differences in length and profile of length distribution were observed in complementarity determining region 3 (CDR3) in both CD4+ and CD8+ T cells in TPE. Altered hydrophobicity was demonstrated in CDR3 in CD8+ T cells and a significant imbalance in the TCR usage pattern of T cells with preferential expression of TRBV4-1 in TPE. A significant increase in clonality was observed in TCR repertoires in CD4+ T cells, but not in CD8+ T cells, although both enriched CD4+ and CD8+ T cells showed TH1 and cytotoxic signatures. Furthermore, we identified a new subset of polyfunctional CD4+ T cells with CD1-restricted, TH1, and cytotoxic characteristics, and this subset might provide protective immunity against Mtb. |
| first_indexed | 2024-04-11T17:59:19Z |
| format | Article |
| id | doaj.art-fc6e6976460343dfbbfa0e015d42580c |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-11T17:59:19Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-fc6e6976460343dfbbfa0e015d42580c2022-12-22T04:10:35ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-02-011310.3389/fmicb.2022.829694829694T Cell Receptor Repertoire Analysis Reveals Signatures of T Cell Responses to Human Mycobacterium tuberculosisMing-Ming Shao0Feng-Shuang Yi1Zhong-Yin Huang2Peng Peng3Feng-Yao Wu4Huan-Zhong Shi5Kan Zhai6Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, ChinaDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, ChinaDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, ChinaDepartment of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan Institute for Tuberculosis Control, Wuhan, ChinaDepartment of Tuberculosis, Nanning Fourth People’s Hospital, Nanning, ChinaDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, ChinaDepartment of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, ChinaCharacterization of T cell receptor (TCR) repertoires is essential for understanding the mechanisms of Mycobacterium tuberculosis (Mtb) infection involving T cell adaptive immunity. The characteristics of TCR sequences and distinctive signatures of T cell subsets in tuberculous patients are still unclear. By combining single-cell TCR sequencing (sc-TCR seq) with single-cell RNA sequencing (sc-RNA seq) and flow cytometry to characterize T cells in tuberculous pleural effusions (TPEs), we identified 41,718 CD3+ T cells in TPEs and paired blood samples, including 30,515 CD4+ T cells and 11,203 CD8+ T cells. Compared with controls, no differences in length and profile of length distribution were observed in complementarity determining region 3 (CDR3) in both CD4+ and CD8+ T cells in TPE. Altered hydrophobicity was demonstrated in CDR3 in CD8+ T cells and a significant imbalance in the TCR usage pattern of T cells with preferential expression of TRBV4-1 in TPE. A significant increase in clonality was observed in TCR repertoires in CD4+ T cells, but not in CD8+ T cells, although both enriched CD4+ and CD8+ T cells showed TH1 and cytotoxic signatures. Furthermore, we identified a new subset of polyfunctional CD4+ T cells with CD1-restricted, TH1, and cytotoxic characteristics, and this subset might provide protective immunity against Mtb.https://www.frontiersin.org/articles/10.3389/fmicb.2022.829694/fullTCR repertoiresingle-cell sequencingtuberculous patientspolyfunctional CD4+ T cellsTRBV4-1 |
| spellingShingle | Ming-Ming Shao Feng-Shuang Yi Zhong-Yin Huang Peng Peng Feng-Yao Wu Huan-Zhong Shi Kan Zhai T Cell Receptor Repertoire Analysis Reveals Signatures of T Cell Responses to Human Mycobacterium tuberculosis Frontiers in Microbiology TCR repertoire single-cell sequencing tuberculous patients polyfunctional CD4+ T cells TRBV4-1 |
| title | T Cell Receptor Repertoire Analysis Reveals Signatures of T Cell Responses to Human Mycobacterium tuberculosis |
| title_full | T Cell Receptor Repertoire Analysis Reveals Signatures of T Cell Responses to Human Mycobacterium tuberculosis |
| title_fullStr | T Cell Receptor Repertoire Analysis Reveals Signatures of T Cell Responses to Human Mycobacterium tuberculosis |
| title_full_unstemmed | T Cell Receptor Repertoire Analysis Reveals Signatures of T Cell Responses to Human Mycobacterium tuberculosis |
| title_short | T Cell Receptor Repertoire Analysis Reveals Signatures of T Cell Responses to Human Mycobacterium tuberculosis |
| title_sort | t cell receptor repertoire analysis reveals signatures of t cell responses to human mycobacterium tuberculosis |
| topic | TCR repertoire single-cell sequencing tuberculous patients polyfunctional CD4+ T cells TRBV4-1 |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.829694/full |
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