Regulation of TCRβ allelic exclusion by gene segment proximity and accessibility.

Regulation of TCRb Allelic Exclusion by Gene Segment Proximity and Accessibility

TCR Feedback Signals Inhibit the Coupling of Recombinationally Accessible V14 Segments with DJ Complexes

Antigen receptor allelic exclusion is thought to occur through mono-allelic initiation and subsequent feedback inhibition of recombinational accessibility. However, our previous analysis of mice containing a V(D)J recombination reporter inserted into Vβ14 (Vβ14Rep) indicated that Vβ14 chromatin accessibility is bi-allelic. To determine whether Vβ14 recombinational accessibility is subject to fe...

The ataxia telangiectasia mutated and cyclin D3 proteins cooperate to help enforce TCRβ and IgH allelic exclusion.

Coordination of V rearrangements between loci on homologous chromosomes is critical for Ig and TCR allelic exclusion. The Ataxia Telangietasia mutated (ATM) protein kinase promotes DNA repair and activates checkpoints to suppress aberrant Ig and TCR rearrangements. In response to RAG cleavage of Igκ loci, ATM inhibits RAG expression and suppresses further Vκ-to-Jκ rearrangements to enforce Igκ ...

Bi-Allelic TCRα or β Recombination Enhances T Cell Development but Is Dispensable for Antigen Responses and Experimental Autoimmune Encephalomyelitis.

Dual TCRα-expressing T cells outnumber dual TCRβ-expressing cells by ~10:1. As a result, efforts to understand how dual TCR T cells impact immunity have focused on dual TCRα expression; dual TCRβ expression remains understudied. We recently demonstrated, however, that dual TCRβ expression accelerated disease in a TCR transgenic model of autoimmune arthritis through enhanced positive selection e...

Regulation of T cell receptor beta gene rearrangements and allelic exclusion by the helix-loop-helix protein, E47.

Allelic exclusion of antigen-receptor genes is ensured primarily by monoallelic locus activation upon rearrangement and subsequently by feedback inhibition of continued rearrangement. Here, we demonstrated that the basic helix-loop-helix protein, E47, promoted T cell receptor beta (TCRbeta) gene rearrangement by directly binding to target gene segments to increase chromatin accessibility in a d...