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Publication : Inefficient V(D)J recombination underlies monogenic T cell receptor β expression.

First Author  Wu GS Year  2020
Journal  Proc Natl Acad Sci U S A Volume  117
Issue  31 Pages  18172-18174
PubMed ID  32690689 Mgi Jnum  J:299475
Mgi Id  MGI:6449948 Doi  10.1073/pnas.2010077117
Citation  Wu GS, et al. (2020) Inefficient V(D)J recombination underlies monogenic T cell receptor beta expression. Proc Natl Acad Sci U S A 117(31):18172-18174
abstractText  The assembly of T cell receptor (TCR) and immunoglobulin (Ig) genes by V(D)J recombination generates the antigen receptor (AgR) diversity that is vital for adaptive immunity. At most AgR loci, V(D)J recombination is regulated so that only one allele assembles a functional gene, ensuring that nearly every T and B cell expresses a single type, or specificity, of AgR. The genomic organizations of some AgR loci permit the assembly and expression of two distinct genes on each allele; however, this is prevented by undetermined mechanisms. We show that the poor qualities of recombination signal sequences (RSSs) flanking Vbeta gene segments suppress the assembly and expression of two distinct TCRbeta genes from a single allele. Our data demonstrate that an intrinsic genetic mechanism that stochastically limits Vbeta recombination efficiency governs monogenic TCRbeta expression, thereby restraining the expression of multiple AgRs on alphabeta T cells.
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