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Functionally specialized human CD4+ T-cell subsets express physicochemically distinct TCRs
oleh: Sofya A Kasatskaya, Kristin Ladell, Evgeniy S Egorov, Kelly L Miners, Alexey N Davydov, Maria Metsger, Dmitry B Staroverov, Elena K Matveyshina, Irina A Shagina, Ilgar Z Mamedov, Mark Izraelson, Pavel V Shelyakin, Olga V Britanova, David A Price, Dmitriy M Chudakov
Format: | Article |
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Diterbitkan: | eLife Sciences Publications Ltd 2020-12-01 |
Deskripsi
The organizational integrity of the adaptive immune system is determined by functionally discrete subsets of CD4+ T cells, but it has remained unclear to what extent lineage choice is influenced by clonotypically expressed T-cell receptors (TCRs). To address this issue, we used a high-throughput approach to profile the αβ TCR repertoires of human naive and effector/memory CD4+ T-cell subsets, irrespective of antigen specificity. Highly conserved physicochemical and recombinatorial features were encoded on a subset-specific basis in the effector/memory compartment. Clonal tracking further identified forbidden and permitted transition pathways, mapping effector/memory subsets related by interconversion or ontogeny. Public sequences were largely confined to particular effector/memory subsets, including regulatory T cells (Tregs), which also displayed hardwired repertoire features in the naive compartment. Accordingly, these cumulative repertoire portraits establish a link between clonotype fate decisions in the complex world of CD4+ T cells and the intrinsic properties of somatically rearranged TCRs.