APMAT analysis reveals the association between CD8 T cell receptors, cognate antigen, and T cell phenotype and persistence
Abstract Elucidating the relationships between a class I peptide antigen, a CD8 T cell receptor (TCR) specific to that antigen, and the T cell phenotype that emerges following antigen stimulation, remains a mostly unsolved problem, largely due to the lack of large data sets that can be mined to reso...
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| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56659-3 |
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| author | Jingyi Xie Daniel G. Chen William Chour Rachel H. Ng Rongyu Zhang Dan Yuan Jongchan Choi Michaela McKasson Pamela Troisch Brett Smith Lesley Jones Andrew Webster Yusuf Rasheed Sarah Li Rick Edmark Sunga Hong Kim M. Murray Jennifer K. Logue Nicholas M. Franko Christopher G. Lausted Brian Piening Heather Algren Julie Wallick Andrew T. Magis Kino Watanabe Phil Mease Philip D. Greenberg Helen Chu Jason D. Goldman Yapeng Su James R. Heath |
| author_facet | Jingyi Xie Daniel G. Chen William Chour Rachel H. Ng Rongyu Zhang Dan Yuan Jongchan Choi Michaela McKasson Pamela Troisch Brett Smith Lesley Jones Andrew Webster Yusuf Rasheed Sarah Li Rick Edmark Sunga Hong Kim M. Murray Jennifer K. Logue Nicholas M. Franko Christopher G. Lausted Brian Piening Heather Algren Julie Wallick Andrew T. Magis Kino Watanabe Phil Mease Philip D. Greenberg Helen Chu Jason D. Goldman Yapeng Su James R. Heath |
| author_sort | Jingyi Xie |
| collection | DOAJ |
| description | Abstract Elucidating the relationships between a class I peptide antigen, a CD8 T cell receptor (TCR) specific to that antigen, and the T cell phenotype that emerges following antigen stimulation, remains a mostly unsolved problem, largely due to the lack of large data sets that can be mined to resolve such relationships. Here, we describe Antigen-TCR Pairing and Multiomic Analysis of T-cells (APMAT), an integrated experimental-computational framework designed for the high-throughput capture and analysis of CD8 T cells, with paired antigen, TCR sequence, and single-cell transcriptome. Starting with 951 putative antigens representing a comprehensive survey of the SARS-CoV-2 viral proteome, we utilize APMAT for the capture and single cell analysis of CD8 T cells from 62 HLA A*02:01 COVID-19 participants. We leverage this comprehensive dataset to integrate with peptide antigen properties, TCR CDR3 sequences, and T cell phenotypes to show that distinct physicochemical features of the antigen-TCR pairs strongly associate with both T cell phenotype and T cell persistence. This analysis suggests that CD8 T cell phenotype following antigen stimulation is at least partially deterministic, rather than the result of stochastic biological properties. |
| format | Article |
| id | doaj-art-da5e75640a2d44a3a1cf871c0e60c8b8 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-da5e75640a2d44a3a1cf871c0e60c8b82025-02-09T12:45:23ZengNature PortfolioNature Communications2041-17232025-02-0116111510.1038/s41467-025-56659-3APMAT analysis reveals the association between CD8 T cell receptors, cognate antigen, and T cell phenotype and persistenceJingyi Xie0Daniel G. Chen1William Chour2Rachel H. Ng3Rongyu Zhang4Dan Yuan5Jongchan Choi6Michaela McKasson7Pamela Troisch8Brett Smith9Lesley Jones10Andrew Webster11Yusuf Rasheed12Sarah Li13Rick Edmark14Sunga Hong15Kim M. Murray16Jennifer K. Logue17Nicholas M. Franko18Christopher G. Lausted19Brian Piening20Heather Algren21Julie Wallick22Andrew T. Magis23Kino Watanabe24Phil Mease25Philip D. Greenberg26Helen Chu27Jason D. Goldman28Yapeng Su29James R. Heath30Institute for Systems BiologyInstitute for Systems BiologyInstitute for Systems BiologyInstitute for Systems BiologyInstitute for Systems BiologyInstitute for Systems BiologyInstitute for Systems BiologyInstitute for Systems BiologyInstitute for Systems BiologyInstitute for Systems BiologyInstitute for Systems BiologyInstitute for Systems BiologyInstitute for Systems BiologyInstitute for Systems BiologyInstitute for Systems BiologyInstitute for Systems BiologyInstitute for Systems BiologyDepartment of Medicine, Allergy and Infectious Diseases, University of WashingtonDepartment of Medicine, Allergy and Infectious Diseases, University of WashingtonInstitute for Systems BiologyProvidence Health & ServicesProvidence Health & ServicesProvidence Health & ServicesInstitute for Systems BiologyDepartment of Medicine, Allergy and Infectious Diseases, University of WashingtonProvidence Swedish Medical CenterFred Hutchinson Cancer CenterDepartment of Medicine, Allergy and Infectious Diseases, University of WashingtonFred Hutchinson Cancer CenterInstitute for Systems BiologyInstitute for Systems BiologyAbstract Elucidating the relationships between a class I peptide antigen, a CD8 T cell receptor (TCR) specific to that antigen, and the T cell phenotype that emerges following antigen stimulation, remains a mostly unsolved problem, largely due to the lack of large data sets that can be mined to resolve such relationships. Here, we describe Antigen-TCR Pairing and Multiomic Analysis of T-cells (APMAT), an integrated experimental-computational framework designed for the high-throughput capture and analysis of CD8 T cells, with paired antigen, TCR sequence, and single-cell transcriptome. Starting with 951 putative antigens representing a comprehensive survey of the SARS-CoV-2 viral proteome, we utilize APMAT for the capture and single cell analysis of CD8 T cells from 62 HLA A*02:01 COVID-19 participants. We leverage this comprehensive dataset to integrate with peptide antigen properties, TCR CDR3 sequences, and T cell phenotypes to show that distinct physicochemical features of the antigen-TCR pairs strongly associate with both T cell phenotype and T cell persistence. This analysis suggests that CD8 T cell phenotype following antigen stimulation is at least partially deterministic, rather than the result of stochastic biological properties.https://doi.org/10.1038/s41467-025-56659-3 |
| spellingShingle | Jingyi Xie Daniel G. Chen William Chour Rachel H. Ng Rongyu Zhang Dan Yuan Jongchan Choi Michaela McKasson Pamela Troisch Brett Smith Lesley Jones Andrew Webster Yusuf Rasheed Sarah Li Rick Edmark Sunga Hong Kim M. Murray Jennifer K. Logue Nicholas M. Franko Christopher G. Lausted Brian Piening Heather Algren Julie Wallick Andrew T. Magis Kino Watanabe Phil Mease Philip D. Greenberg Helen Chu Jason D. Goldman Yapeng Su James R. Heath APMAT analysis reveals the association between CD8 T cell receptors, cognate antigen, and T cell phenotype and persistence Nature Communications |
| title | APMAT analysis reveals the association between CD8 T cell receptors, cognate antigen, and T cell phenotype and persistence |
| title_full | APMAT analysis reveals the association between CD8 T cell receptors, cognate antigen, and T cell phenotype and persistence |
| title_fullStr | APMAT analysis reveals the association between CD8 T cell receptors, cognate antigen, and T cell phenotype and persistence |
| title_full_unstemmed | APMAT analysis reveals the association between CD8 T cell receptors, cognate antigen, and T cell phenotype and persistence |
| title_short | APMAT analysis reveals the association between CD8 T cell receptors, cognate antigen, and T cell phenotype and persistence |
| title_sort | apmat analysis reveals the association between cd8 t cell receptors cognate antigen and t cell phenotype and persistence |
| url | https://doi.org/10.1038/s41467-025-56659-3 |
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