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APMAT analysis reveals the association between CD8 T cell receptors, cognate antigen, and T cell phenotype and persistence.

Title: APMAT analysis reveals the association between CD8 T cell receptors, cognate antigen, and T cell phenotype and persistence.
Authors: Liang, JingXin; Chen, Daniel G; Chour, William; Ng, Rachel H; Zhang, Rongyu; Yuan, Dan; Choi, Jongchan; McKasson, Michaela; Troisch, Pamela; Smith, Brett; Jones, Lesley; Webster, Andrew; Rasheed, Yusuf; Li, Sarah; Edmark, Rick; Hong, Sunga; Murray, Kim M; Logue, Jennifer K; Franko, Nicholas M; Lausted, Christopher G; Piening, Brian D.; Algren, Heather A; Wallick, Julie A; Magis, Andrew T; Watanabe, Kino; Mease, Philip; Greenberg, Philip D; Chu, Helen; Goldman, Jason D; Su, Yapeng; Heath, James R
Source: Articles, Abstracts, and Reports
Publisher Information: Providence Digital Commons
Publication Year: 2025
Collection: Providence St. Joseph Health Digital Commons
Subject Terms: washington; isb; seattle; swedish; genomics; covid-19
Description: 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 unique, 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.
Document Type: text
Language: unknown
Relation: https://digitalcommons.providence.org/publications/9579; https://www.ncbi.nlm.nih.gov/pubmed/39829843
DOI: 10.1101/2025.01.08.631993
Availability: https://digitalcommons.providence.org/publications/9579; https://doi.org/10.1101/2025.01.08.631993; https://www.ncbi.nlm.nih.gov/pubmed/39829843
Accession Number: edsbas.15EA3015
Database: BASE