A framework for highly multiplexed dextramer mapping and prediction of T cell receptor sequences to antigen specificity.

Zhang, Wen, Hawkins, Peter G, He, Jing, Gupta, Namita T, Liu, Jinrui, Choonoo, Gabrielle, Jeong, Se W, Chen, Calvin R, Dhanik, Ankur, Dillon, Myles, Deering, Raquel, Macdonald, Lynn E, Thurston, Gavin, Atwal, Gurinder S (May 2021) A framework for highly multiplexed dextramer mapping and prediction of T cell receptor sequences to antigen specificity. Science Advances, 7 (20). eabf5835-eabf5835. ISSN 2375-2548

[img] PDF
2021.Zhang.tcell_receptor.pdf
Available under License Creative Commons Attribution Non-commercial.

Download (4MB)
URL: https://www.ncbi.nlm.nih.gov/pubmed/33990328
DOI: 10.1126/sciadv.abf5835

Abstract

T cell receptor (TCR) antigen-specific recognition is essential for the adaptive immune system. However, building a TCR-antigen interaction map has been challenging due to the staggering diversity of TCRs and antigens. Accordingly, highly multiplexed dextramer-TCR binding assays have been recently developed, but the utility of the ensuing large datasets is limited by the lack of robust computational methods for normalization and interpretation. Here, we present a computational framework comprising a novel method, ICON (Integrative COntext-specific Normalization), for identifying reliable TCR-pMHC (peptide-major histocompatibility complex) interactions and a neural network-based classifier TCRAI that outperforms other state-of-the-art methods for TCR-antigen specificity prediction. We further demonstrated that by combining ICON and TCRAI, we are able to discover novel subgroups of TCRs that bind to a given pMHC via different mechanisms. Our framework facilitates the identification and understanding of TCR-antigen-specific interactions for basic immunological research and clinical immune monitoring.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell
CSHL Authors:
Communities: CSHL labs > Atwal lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: May 2021
Date Deposited: 24 Jun 2021 19:05
Last Modified: 24 Jun 2021 19:05
PMCID: PMC8121425
URI: https://repository.cshl.edu/id/eprint/40229

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving