T cell differentiation and lineage choice are determined by the TCR

Journal Contribution ResearchOnline@JCU
Miles, John;Watkins, Thomas;Darko, Sam;Wijaya, Kuatrinnus;Cooper, Martha;Ransier, Amy;Waardenberg, Ashley;Amante, Fiona;Mccarthy, James;Price, David;Burrows, Scott;Doolan, Denise;Field, Matt;Douek, Daniel
Abstract

Next-generation sequencing technologies have revealed that adaptive immunity is underpinned by a vast array of T cell receptors (TCRs). However, it has proven difficult to interpret these extensive datasets, in part because the field previously lacked a comprehensive and internally controlled reference atlas encompassing the full spectrum of phenotypically defined subsets in each lineage. To address this knowledge gap, we sequenced 74 million TCRs expressed by discrete CD4+ and CD8+ memory T cell populations across genetically unrelated individuals, providing a resource to inform basic and applied studies of repertoire compartmentalisation within the adaptive immune system. Using this resource, we found that T cell differentiation could not be explained solely by the self-renewing effector model and, unexpectedly, that T cell fate could be predicted by specific genetic and physicochemical features of the TCR.

Journal

FASEB Journal

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Volume

36

ISBN/ISSN

1530-6860

Edition

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Issue

S1

Pages Count

3

Location

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Publisher

John Wiley & Sons, Inc.

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Publisher Location

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Publish Date

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Url

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Date

N/A

EISSN

N/A

DOI

10.1096/fasebj.2022.36.S1.R6136