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Viral infection reveals hidden sharing of TCR CDR3 sequences between individuals

Mark, Michal; Reich-Zeliger, Shlomit; Greenstein, Erez; Biram, Adi; Chain, Benny; Friedman, Nir; Madi, Asaf; (2023) Viral infection reveals hidden sharing of TCR CDR3 sequences between individuals. Frontiers in Immunology , 14 , Article 1199064. 10.3389/fimmu.2023.1199064. Green open access

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Abstract

The T cell receptor is generated by a process of random and imprecise somatic recombination. The number of possible T cell receptors which this process can produce is enormous, greatly exceeding the number of T cells in an individual. Thus, the likelihood of identical TCRs being observed in multiple individuals (public TCRs) might be expected to be very low. Nevertheless such public TCRs have often been reported. In this study we explore the extent of TCR publicity in the context of acute resolving Lymphocytic choriomeningitis virus (LCMV) infection in mice. We show that the repertoire of effector T cells following LCMV infection contains a population of highly shared TCR sequences. This subset of TCRs has a distribution of naive precursor frequencies, generation probabilities, and physico-chemical CDR3 properties which lie between those of classic public TCRs, which are observed in uninfected repertoires, and the dominant private TCR repertoire. We have named this set of sequences "hidden public" TCRs, since they are only revealed following infection. A similar repertoire of hidden public TCRs can be observed in humans after a first exposure to SARS-COV-2. The presence of hidden public TCRs which rapidly expand following viral infection may therefore be a general feature of adaptive immunity, identifying an additional level of inter-individual sharing in the TCR repertoire which may form an important component of the effector and memory response.

Type: Article
Title: Viral infection reveals hidden sharing of TCR CDR3 sequences between individuals
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fimmu.2023.1199064
Publisher version: http://dx.doi.org/10.3389/fimmu.2023.1199064
Language: English
Additional information: Copyright © 2023 Mark, Reich-Zeliger, Greenstein, Biram, Chain, Friedman and Madi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: LCMV (lymphocytic choriomeningitis virus), TCR - T cell receptor, effector T cells, epitope-specific T cell, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10172164
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