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Inefficient V(D)J recombination underlies monogenic T cell receptor β expression
Glendon S Wu1,2, Craig H Bassing3,2
1Immunology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Summary
T cell receptor (TCR) gene assembly ensures adaptive immunity by limiting antigen receptor (AgR) expression to a single specificity. Poor quality recombination signal sequences (RSSs) on TCR beta genes prevent dual gene expression from one allele.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- V(D)J recombination assembles T cell receptor (TCR) and immunoglobulin (Ig) genes, creating essential antigen receptor (AgR) diversity for adaptive immunity.
- Typically, only one allele assembles a functional gene, ensuring T and B cells express a single AgR specificity.
- Mechanisms preventing dual gene expression from some AgR loci remain unclear.
Purpose of the Study:
- To investigate the mechanisms limiting the expression of two distinct TCR beta genes from a single allele.
- To understand how V(D)J recombination efficiency influences monogenic TCR beta expression.
Main Methods:
- Analysis of recombination signal sequences (RSSs) flanking Vβ gene segments.
- Assessment of TCR beta gene assembly and expression.
- Investigating stochastic limitations in Vβ recombination efficiency.
Main Results:
- Poor quality RSSs associated with Vβ gene segments suppress the assembly and expression of two distinct TCR beta genes on a single allele.
- An intrinsic genetic mechanism limits Vβ recombination efficiency stochastically.
- This stochastic limitation governs monogenic TCR beta expression.
Conclusions:
- The quality of RSSs plays a critical role in regulating TCR beta gene allelic exclusion.
- Stochastic control of Vβ recombination efficiency ensures monogenic TCR beta expression.
- This mechanism prevents the expression of multiple AgRs on αβ T cells, maintaining immune specificity.
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