Detecting T cell receptors involved in immune responses from single repertoire snapshots

Pogorelyy, Mikhail V. and Minervina, Anastasia A. and Shugay, Mikhail and Chudakov, Dmitriy M. and Lebedev, Yuri B. and Mora, Thierry and Walczak, Aleksandra M. and Freeman, Thomas C. (2019) Detecting T cell receptors involved in immune responses from single repertoire snapshots. PLOS Biology, 17 (6). e3000314. ISSN 1545-7885

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Abstract

Hypervariable T cell receptors (TCRs) play a key role in adaptive immunity, recognizing a vast diversity of pathogen-derived antigens. Our ability to extract clinically relevant information from large high-throughput sequencing of TCR repertoires (RepSeq) data is limited, because little is known about TCR–disease associations. We present Antigen-specific Lymphocyte Identification by Clustering of Expanded sequences (ALICE), a statistical approach that identifies TCR sequences actively involved in current immune responses from a single RepSeq sample and apply it to repertoires of patients with a variety of disorders — patients with autoimmune disease (ankylosing spondylitis [AS]), under cancer immunotherapy, or subject to an acute infection (live yellow fever [YF] vaccine). We validate the method with independent assays. ALICE requires no longitudinal data collection nor large cohorts, and it is directly applicable to most RepSeq datasets. Its results facilitate the identification of TCR variants associated with diseases and conditions, which can be used for diagnostics and rational vaccine design.

Item Type: Article
Subjects: AP Academic Press > Biological Science
Depositing User: Unnamed user with email support@apacademicpress.com
Date Deposited: 12 Jan 2023 10:00
Last Modified: 25 Apr 2024 08:57
URI: http://info.openarchivespress.com/id/eprint/214

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