APMAT analysis reveals the association between CD8 T cell receptors, cognate antigen, and T cell phenotype and persistence.
Publication Title
Nat Commun
Document Type
Article
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
