RT Journal Article
SR Electronic
T1 Population based selection shapes the T cell receptor repertoire during thymic development
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.02.14.480309
DO 10.1101/2022.02.14.480309
A1 Camaglia, Francesco
A1 Ryvkin, Arie
A1 Greenstein, Erez
A1 Reich-Zeliger, Shlomit
A1 Chain, Benny
A1 Mora, Thierry
A1 Walczak, Aleksandra M.
A1 Friedman, Nir
YR 2022
UL http://biorxiv.org/content/early/2022/02/15/2022.02.14.480309.abstract
AB One of the feats of adaptive immunity is its ability to recognize foreign pathogens while sparing the self. During maturation in the thymus, T cells are selected through the binding properties of their antigen-specific T-cell receptor (TCR), through the elimination of both weakly (positive selection) and strongly (negative selection) self-reactive receptors. However, the impact of thymic selection on the TCR repertoire is poorly understood. Here, we use transgenic Nur77-mice expressing a T-cell activation reporter to study the repertoires of thymic T cells at various stages of their development, including cells that do not pass selection. We combine high-throughput repertoire sequencing with statistical inference techniques to charactarize the selection of the TCR in these distinct subsets. We find small but significant differences in the TCR repertoire parameters between the maturation stages, which recapitulate known differentiation pathways leading to the CD4+ and CD8+ subtypes. These differences can be simulated by simple models of selection acting linearly on the sequence features. We find no evidence of specific sequences or sequence motifs or features that are suppressed by negative selection. These results are consistent with a collective or statistical model for T-cell specificity, where negative selection biases the repertoire away from self recognition, rather than ensuring lack of self-reactivity at the single-cell level.Competing Interest StatementThe authors have declared no competing interest.