Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
J Immunol. 2011 Dec 15;187(12):6374-81. doi: 10.4049/jimmunol.1102611. Epub 2011 Nov 11.
Ag receptor loci are regulated to promote allelic exclusion, but the mechanisms are not well understood. Assembly of a functional TCR β-chain gene triggers feedback inhibition of V(β)-to-DJ(β) recombination in double-positive (DP) thymocytes, which correlates with reduced V(β) chromatin accessibility and a locus conformational change that separates V(β) from DJ(β) gene segments. We previously generated a Tcrb allele that maintained V(β) accessibility but was still subject to feedback inhibition in DP thymocytes. We have now further analyzed the contributions of chromatin accessibility and locus conformation to feedback inhibition using two novel TCR alleles. We show that reduced V(β) accessibility and increased distance between V(β) and DJ(β) gene segments both enforce feedback inhibition in DP thymocytes.
Ag 受体基因座受到调控以促进等位基因排斥，但机制尚不清楚。功能性 TCRβ 链基因的组装会触发双阳性 (DP) 胸腺细胞中 V(β)-到-DJ(β)重组的反馈抑制，这与 V(β)染色质可及性降低以及导致 V(β)与 DJ(β)基因片段分离的基因座构象变化相关。我们之前生成了一个 Tcrb 等位基因，该基因保持了 V(β)的可及性，但在 DP 胸腺细胞中仍受到反馈抑制。我们现在使用两个新的 TCR 等位基因进一步分析了染色质可及性和基因座构象对反馈抑制的贡献。我们表明，V(β)的可及性降低和 V(β)与 DJ(β)基因片段之间的距离增加都会在 DP 胸腺细胞中强制实施反馈抑制。
