AUTHOR=Levi Reut , Louzoun Yoram 

TITLE=Two Step Selection for Bias in β Chain V-J Pairing

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.906217

DOI=10.3389/fimmu.2022.906217

ISSN=1664-3224

ABSTRACT=<p>The <italic>β</italic> chain rearrangement in T cells is a two-step process where first <italic>D<sub>β</sub></italic> and <italic>J<sub>β</sub></italic> bind, and only then <italic>V<sub>β</sub></italic> is joined to the complex. We here show that the frequency of human and mouse <italic>V<sub>β</sub>
J<sub>β</sub></italic> combinations deviates from the one expected based on each gene usage frequency. This bias is observed mainly in functional (F) rearrangements, but also slightly in non-functional (NF) rearrangements. Preferred <italic>V<sub>β</sub>
J<sub>β</sub></italic> combinations in F clones are shared between donors and samples, suggesting a common structural mechanism for these biases in addition to any host-specific antigen-induced peripheral selection. The sharing holds even in clones with J<italic><sub>β</sub></italic>1 that share the same <italic>D<sub>β</sub></italic>1 gene. <italic>V<sub>β</sub>
J<sub>β</sub></italic> usage is correlated with the Molecular Weight and Isoelectric Point in F clones. The pairing is also observed in the Double Positive cells in mice thymocytes, suggesting that the selection leading to such a pairing occurs before thymic selection. These results suggest an additional structural checkpoint in the beta chain development prior to thymic selection during the T cell receptor expression. Understanding this structural selection is important for the distinction between normal and aberrant T cell development, and crucial for the design of engineered TCRs.</p>