APMAT analysis reveals the association between CD8 T cell receptors, cognate antigen, and T cell phenotype and persistence
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.
Authors
- Julie A. Wallick (ORCID: https://orcid.org/0000-0002-4568-4704)
- Jingyi Xie (ORCID: https://orcid.org/0000-0002-8959-4268)
- Helen Y. Chu (ORCID: https://orcid.org/0000-0001-8502-9600)
- Sunga Hong (ORCID: https://orcid.org/0000-0003-4412-2811)
- Lesley Jones
- Jason D. Goldman (ORCID: https://orcid.org/0000-0002-3825-6832)
- Nicholas Franko (ORCID: https://orcid.org/0000-0001-8165-6332)
- Philip D. Greenberg (ORCID: https://orcid.org/0000-0003-3812-647X)
- James R. Heath (ORCID: https://orcid.org/0000-0001-5356-4385)
- Andrew T. Magis (ORCID: https://orcid.org/0000-0003-0576-677X)
- Sarah Li (ORCID: https://orcid.org/0000-0002-6424-5483)
- William Chour (ORCID: https://orcid.org/0000-0003-1817-0123)
- Pamela Troisch
- Kim M. Murray
- Christopher Lausted (ORCID: https://orcid.org/0000-0003-3073-9212)
- Jennifer K. Logue (ORCID: https://orcid.org/0000-0002-7889-8960)
- Yusuf Rasheed (ORCID: https://orcid.org/0000-0003-2979-3473)
- Heather A. Algren (ORCID: https://orcid.org/0000-0003-0703-1873)
- P.J. Mease
- Yapeng Su (ORCID: https://orcid.org/0000-0002-6305-8467)
- Rick Edmark
- Brian Piening (ORCID: https://orcid.org/0000-0002-2683-8157)
- Kino Watanabe
- Daniel Chen (ORCID: https://orcid.org/0000-0001-6660-6257)
- Dan Yuan (ORCID: https://orcid.org/0000-0001-9651-8020)
- Andrew Webster (ORCID: https://orcid.org/0000-0003-3420-8689)
- Brett Smith (ORCID: https://orcid.org/0000-0002-2586-5014)
- Rongyu Zhang (ORCID: https://orcid.org/0000-0001-7361-9152)
- Jongchan Choi (ORCID: https://orcid.org/0000-0003-0394-9978)
- Raymond T. Ng (ORCID: https://orcid.org/0000-0003-3692-8524)
- Michaela McKasson
Institutions
- Providence College (US)
- University of Washington (US)
- Institute for Systems Biology (US)
- Fred Hutch Cancer Center (US)
- Swedish Medical Center (US)
- Providence Health & Services (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-02-06
- DOI
- https://doi.org/10.1038/s41467-025-56659-3
- Citations
- 6
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 4.78
Funders
- Damon Runyon Cancer Research Foundation
- Parker Institute for Cancer Immunotherapy
- National Institutes of Health
- Biomedical Advanced Research and Development Authority
- National Cancer Institute