A set point in the selection of the αβTCR T cell repertoire imposed by pre-TCR signaling strength

E. Bovolenta, E. M. García-Cuesta, L. Horndler, J. Ponomarenko, W.W. Schamel, M. Mellado, M. Castro, D. Abia, H.M. Van Santen

Proceedings of the National Academy of Sciences of the United States of America Vol. 119, nº. 22, pp. e2201907119-1 - e2201907119-9

Summary:

Signaling via the T cell receptor (TCR) is critical during the development, maintenance, and activation of T cells. Quantitative aspects of TCR signaling have an important role during positive and negative selection, lineage choice, and ability to respond to small amounts of antigen. By using a mutant mouse line expressing a hypomorphic allele of the CD3ζ chain, we show here that the strength of pre-TCR–mediated signaling during T cell development determines the diversity of the TCRβ repertoire available for positive and negative selection, and hence of the final αβTCR repertoire. This finding uncovers an unexpected, pre-TCR signaling–dependent and repertoire–shaping role for β-selection beyond selection of in-frame rearranged TCRβ chains. Our data furthermore support a model of pre-TCR signaling in which the arrangement of this receptor in stable nanoclusters determines its quantitative signaling capacity.

Spanish layman's summary:

Mediante un análisis basado en la recombinación de ADN, citometría, secuenciación de ARN y modelos matemáticos, proporcionamos evidencia sobre el instante en el que se genera la diversidad del TCR, sorprendentemente en las primeras fases de maduración de células T en el timo.

 

English layman's summary:

Using recombinant DNA analysis, cytometry, RNA sequencing, and mathematical modeling, we provide evidence on the timing of TCR diversity, surprisingly early in the maturation of T cells in the thymus.

 

JCR Impact Factor and WoS quartile: 11,100 - Q1 (2022)

DOI reference: https://doi.org/10.1073/pnas.2201907119

Published on paper: May 2022.

Published on-line: May 2022.

Citation:
E. Bovolenta, E. M. García-Cuesta, L. Horndler, J. Ponomarenko, W.W. Schamel, M. Mellado, M. Castro, D. Abia, H.M. Van Santen, A set point in the selection of the αβTCR T cell repertoire imposed by pre-TCR signaling strength. Proceedings of the National Academy of Sciences of the United States of America. Vol. 119, nº. 22, pp. e2201907119-1 - e2201907119-9, May 2022. [Online: May 2022]