Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 117, Issue 31, Pages 18172-18174Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2010077117
Keywords
V(D)J recombination; allelic exclusion; monogenic expression; lymphocyte development; recombination signal sequence
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Funding
- National Institutes of Health [T32 AI055428, R01 AI 130231]
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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 V beta gene segments suppress the assembly and expression of two distinct TCR beta genes from a single allele. Our data demonstrate that an intrinsic genetic mechanism that stochastically limits V beta recombination efficiency governs monogenic TCR beta expression, thereby restraining the expression of multiple AgRs on alpha beta T cells.
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