Shortening of complementarity determining region 3 of the T cell recept or α chain during thymocyte development
Shortening of complementarity determining region 3 of the T cell recept or α chain during thymocyte development
复制标题
胸腺细胞发育过程中 T 细胞受体或 α 链的互补决定区 3 的缩短
DOI：
10.1016/j.molimm.2010.11.003
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发表时间：
2011
期刊：
影响因子：
3.6
通讯作者：
Itoh T
中科院分区：
文献类型：
--
作者：
Matsutani T;Ogata M;Fujii Y;Kitaura K;Nishimoto N;Suzuki R;Itoh T
TCR多样性主要取决于由非种系编码的核苷酸插入和/或缺失产生的高可变互补决定区3 (CDR3) α和β环。众所周知，在胸腺细胞发育过程中，CDR3β序列的长度缩短，这种缩短的程度受到种系编码的Vβ片段或MHC单倍型的强烈影响。为了研究CDR3α是否与CDR3β缩短的程度相同，以及它如何受到Vα片段或MHC单倍型的影响，我们分析了CDR3α在不同品系小鼠（C57BL/6、c . b10和Balb/c）胸腺CD4+CD8+ (DP)、CD4+CD8−(CD4SP)和CD4−CD8+ (CD8SP) T细胞中的长度分布。正如预期的那样，CDR3α在所有测试菌株的CD4SP和CD8SP细胞中都发生缩短，缩短的程度取决于Vα片段的使用。然而，CD4SP和CD8SP细胞中单个Vα片段的CDR3α缩短程度没有相关性。有趣的是，在不同品系的小鼠中，CDR3α缩短的程度仅在CD4SP细胞中存在显著相关性，而在CD8SP细胞中没有，与MHC单倍型无关。这些结果表明，CDR3α缩短的程度主要由种系编码的Vα片段决定，受MHC I类等位基因变异的影响，而MHC II类不受影响。目前的研究表明，在胸腺细胞发育过程中，具有较短CDR3α序列的T细胞更适合用于功能性TCR库，这为TCR和p-MHC配体的相互作用提供了有趣的见解。
TCR diversity depends mainly on the hypervariable complementarity determining region 3 (CDR3) α and β loops generated by non-germline-encoded nucleotide insertions and/or deletions. It is known that the length of the CDR3β sequence shortens during the process of thymocyte development and that the extent of this shortening is strongly affected by germline-encoded Vβ segments or MHC haplotypes. To examine whether CDR3α shortens to the same extent as CDR3β and how it is affected by Vα segments or MHC haplotypes, we analyzed CDR3α length distributions in thymic CD4+CD8+ (DP), CD4+CD8− (CD4SP) and CD4−CD8+ (CD8SP) T cells of different strains of mice (C57BL/6, C.B10 and Balb/c). As expected, CDR3α shortening occurred in both the CD4SP and CD8SP cells of all strains tested and the extent of shortening varied considerably depending on Vα segment use. However, there was no correlation in the extent of CDR3α shortening in individual Vα segments between CD4SP and CD8SP cells. Interestingly, there was a significant correlation in the extent of CDR3α shortening among different strains of mice only in CD4SP but not CD8SP cells, independent of MHC haplotype. These results suggest that the extent of CDR3α shortening is primarily determined by germline-encoded Vα segments and affected by allelic variation of MHC class I but not of MHC class II. The present study showed that T cells with shorter CDR3α sequences are preferably selected for the functional TCR repertoire during thymocyte development, and this provides an intriguing insight into the interactions of the TCR and p-MHC ligand.