APMAT analysis reveals the association between CD8 T cell receptors, cognate antigen, and T cell phenotype and persistence.
Publication Title
Nat Commun
Authors
Jingyi Xie, Institute for Systems Biology, Seattle, WA, 98109, USA.
Daniel G Chen, Institute for Systems Biology, Seattle, WA, 98109, USA.
William Chour, Institute for Systems Biology, Seattle, WA, 98109, USA.
Rachel H Ng, Institute for Systems Biology, Seattle, WA, 98109, USA.
Rongyu Zhang, Institute for Systems Biology, Seattle, WA, 98109, USA.
Dan Yuan, Institute for Systems Biology, Seattle, WA, 98109, USA.
Jongchan Choi, Institute for Systems Biology, Seattle, WA, 98109, USA.
Michaela McKasson, Institute for Systems Biology, Seattle, WA, 98109, USA.
Pamela Troisch, Institute for Systems Biology, Seattle, WA, 98109, USA.
Brett Smith, Institute for Systems Biology, Seattle, WA, 98109, USA.
Lesley Jones, Institute for Systems Biology, Seattle, WA, 98109, USA.
Andrew Webster, Institute for Systems Biology, Seattle, WA, 98109, USA.
Yusuf Rasheed, Institute for Systems Biology, Seattle, WA, 98109, USA.
Sarah Li, Institute for Systems Biology, Seattle, WA, 98109, USA.
Rick Edmark, Institute for Systems Biology, Seattle, WA, 98109, USA.
Sunga Hong, Institute for Systems Biology, Seattle, WA, 98109, USA.
Kim M Murray, Institute for Systems Biology, Seattle, WA, 98109, USA.
Jennifer K Logue
Nicholas M Franko
Christopher G Lausted, Institute for Systems Biology, Seattle, WA, 98109, USA.
Brian Piening, Providence Health & Services, Seattle, WA, 99109, USAFollow
Heather Algren, Providence Health & Services, Providence Swedish Medical Center, Seattle, WA, 98122, USAFollow
Julie Wallick, Providence Swedish Medical Center, Seattle, WA, 98122, USAFollow
Andrew T Magis, Institute for Systems Biology, Seattle, WA, 98109, USA.
Kino Watanabe
Phil Mease, Providence Swedish Medical Center, Seattle, WA, 98122, USAFollow
Philip D Greenberg
Helen Chu
Jason D Goldman, Division of Infectious Diseases Swedish Medical Center Seattle WA.Follow
Yapeng Su, Institute for Systems Biology, Seattle, WA, 98109, USA.
James R Heath, Institute for Systems Biology, Seattle, WA, 98109, USA.Follow
Publication Date
2-6-2025
Keywords
washington; isb; swedish; covid-19; oregon; chiles
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.
Area of Special Interest
Cancer
Specialty/Research Institute
Infectious Diseases
Specialty/Research Institute
Institute for Systems Biology
Specialty/Research Institute
Earle A. Chiles Research Institute
DOI
10.1038/s41467-025-56659-3
