Distinct T-cell receptor (TCR) gene segment usage and MHC-restriction between foetal and adult thymus
Here, we sequenced rearranged TCRβ and TCRα chain sequences in CD4+CD8+ double positive (DP), CD4+CD8- single positive (SP4) and CD4-CD8+ (SP8) thymocyte populations from the foetus and young adult mouse. We found that life-stage had a greater impact on TCRβ and TCRα gene segment usage than cell-typ...
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eLife Sciences Publications Ltd
2024-12-01
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| Online Access: | https://elifesciences.org/articles/93493 |
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| author | Jasmine Rowell Ching-In Lau Susan Ross Diana C Yanez Oscar A Peña Benny Chain Tessa Crompton |
| author_facet | Jasmine Rowell Ching-In Lau Susan Ross Diana C Yanez Oscar A Peña Benny Chain Tessa Crompton |
| author_sort | Jasmine Rowell |
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| description | Here, we sequenced rearranged TCRβ and TCRα chain sequences in CD4+CD8+ double positive (DP), CD4+CD8- single positive (SP4) and CD4-CD8+ (SP8) thymocyte populations from the foetus and young adult mouse. We found that life-stage had a greater impact on TCRβ and TCRα gene segment usage than cell-type. Foetal repertoires showed bias towards 3’TRAV and 5’TRAJ rearrangements in all populations, whereas adult repertoires used more 5’TRAV gene segments, suggesting that progressive TCRα rearrangements occur less frequently in foetal DP cells. When we synchronised young adult DP thymocyte differentiation by hydrocortisone treatment the new recovering DP thymocyte population showed more foetal-like 3’TRAV and 5’TRAJ gene segment usage. In foetus we identified less influence of MHC-restriction on α-chain and β-chain combinatorial VxJ usage and CDR1xCDR2 (V region) usage in SP compared to adult, indicating weaker impact of MHC-restriction on the foetal TCR repertoire. The foetal TCRβ repertoire was less diverse, less evenly distributed, with fewer non-template insertions, and all foetal populations contained more clonotypic expansions than adult. The differences between the foetal and adult thymus TCR repertoires are consistent with the foetal thymus producing αβT-cells with properties and functions that are distinct from adult T-cells: their repertoire is less governed by MHC-restriction, with preference for particular gene segment usage, less diverse with more clonotypic expansions, and more closely encoded by genomic sequence. |
| format | Article |
| id | doaj-art-cad8f80190414a5682a9e4cb024960d6 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-cad8f80190414a5682a9e4cb024960d62024-12-05T14:24:22ZengeLife Sciences Publications LtdeLife2050-084X2024-12-011310.7554/eLife.93493Distinct T-cell receptor (TCR) gene segment usage and MHC-restriction between foetal and adult thymusJasmine Rowell0https://orcid.org/0000-0001-7040-8528Ching-In Lau1Susan Ross2Diana C Yanez3Oscar A Peña4https://orcid.org/0000-0002-2582-0238Benny Chain5https://orcid.org/0000-0002-7417-3970Tessa Crompton6https://orcid.org/0000-0002-8973-4021UCL Great Ormond Street Institute of Child Health, London, United KingdomUCL Great Ormond Street Institute of Child Health, London, United KingdomUCL Great Ormond Street Institute of Child Health, London, United KingdomUCL Great Ormond Street Institute of Child Health, London, United KingdomSchool of Biochemistry, University of Bristol, Bristol, United KingdomDivision of Infection and Immunity, University College London, London, United KingdomUCL Great Ormond Street Institute of Child Health, London, United KingdomHere, we sequenced rearranged TCRβ and TCRα chain sequences in CD4+CD8+ double positive (DP), CD4+CD8- single positive (SP4) and CD4-CD8+ (SP8) thymocyte populations from the foetus and young adult mouse. We found that life-stage had a greater impact on TCRβ and TCRα gene segment usage than cell-type. Foetal repertoires showed bias towards 3’TRAV and 5’TRAJ rearrangements in all populations, whereas adult repertoires used more 5’TRAV gene segments, suggesting that progressive TCRα rearrangements occur less frequently in foetal DP cells. When we synchronised young adult DP thymocyte differentiation by hydrocortisone treatment the new recovering DP thymocyte population showed more foetal-like 3’TRAV and 5’TRAJ gene segment usage. In foetus we identified less influence of MHC-restriction on α-chain and β-chain combinatorial VxJ usage and CDR1xCDR2 (V region) usage in SP compared to adult, indicating weaker impact of MHC-restriction on the foetal TCR repertoire. The foetal TCRβ repertoire was less diverse, less evenly distributed, with fewer non-template insertions, and all foetal populations contained more clonotypic expansions than adult. The differences between the foetal and adult thymus TCR repertoires are consistent with the foetal thymus producing αβT-cells with properties and functions that are distinct from adult T-cells: their repertoire is less governed by MHC-restriction, with preference for particular gene segment usage, less diverse with more clonotypic expansions, and more closely encoded by genomic sequence.https://elifesciences.org/articles/93493thymusTCR sequencingTCR repertoirerepertoire selectionMHC-restrictionT-cell development |
| spellingShingle | Jasmine Rowell Ching-In Lau Susan Ross Diana C Yanez Oscar A Peña Benny Chain Tessa Crompton Distinct T-cell receptor (TCR) gene segment usage and MHC-restriction between foetal and adult thymus eLife thymus TCR sequencing TCR repertoire repertoire selection MHC-restriction T-cell development |
| title | Distinct T-cell receptor (TCR) gene segment usage and MHC-restriction between foetal and adult thymus |
| title_full | Distinct T-cell receptor (TCR) gene segment usage and MHC-restriction between foetal and adult thymus |
| title_fullStr | Distinct T-cell receptor (TCR) gene segment usage and MHC-restriction between foetal and adult thymus |
| title_full_unstemmed | Distinct T-cell receptor (TCR) gene segment usage and MHC-restriction between foetal and adult thymus |
| title_short | Distinct T-cell receptor (TCR) gene segment usage and MHC-restriction between foetal and adult thymus |
| title_sort | distinct t cell receptor tcr gene segment usage and mhc restriction between foetal and adult thymus |
| topic | thymus TCR sequencing TCR repertoire repertoire selection MHC-restriction T-cell development |
| url | https://elifesciences.org/articles/93493 |
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