Functionally specialized human CD4+ T-cell subsets express physicochemically distinct TCRs
Sofya A. Kasatskaya, Kristin Ladell, Evgeniy S. Egorov, Kelly L. Miners, Alexey N. Davydov, Maria Metsger, Dmitriy 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
Abstract
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.