Premium
T cell differentiation and lineage choice are determined by the TCR
Author(s) -
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
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.r6136
Subject(s) - t cell receptor , biology , repertoire , lineage (genetic) , effector , cd8 , acquired immune system , t cell , computational biology , evolutionary biology , genetics , immune system , microbiology and biotechnology , gene , physics , acoustics
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.