Hughes Maureen M, Yassai Maryam, Sedy John R, Wehrly Tara D, Huang Ching-Yu, Kanagawa Osami, Gorski Jack, Sleckman Barry P
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis 63110, USA.
Eur J Immunol. 2003 Jun;33(6):1568-75. doi: 10.1002/eji.200323961.
The third complementarity-determining region (CDR) of the TCR alpha and beta chains forms loops that engage amino acid residues of peptides complexed with MHC. This interaction is central to the specific discrimination of antigenic-peptide-MHC complexes by the TCR. The TCRbeta chain CDR3 loop is encoded by the Dbeta gene segment and flanking portions of the Vbeta and Jbeta gene segments. The joining of these gene segments is imprecise, leading to significant variability in the TCRbeta chain CDR3 loop length and amino acid composition. In marked contrast to other pairing antigen-receptor chains, the TCR beta and alpha chain CDR3 loop size distributions are relatively narrow and closely matched. Thus, pairing of TCR alpha and beta chains with relatively similar CDR3 loop sizes may be important for generating a functional repertoire of alpha beta TCR. Here we show that the TCRbeta chain CDR3 loop size distribution is minimally impacted by TCRbeta chain or alpha beta TCR selection during thymocyte development. Rather, this distribution is determined primarily at the level of variable-region gene assembly, and is critically dependent on unique features of the V(D)J recombination reaction that ensure Dbeta gene segment utilization.
TCRα链和β链的第三个互补决定区（CDR）形成环，与与MHC复合的肽的氨基酸残基相互作用。这种相互作用对于TCR对抗原肽-MHC复合物的特异性识别至关重要。TCRβ链CDR3环由Dβ基因片段以及Vβ和Jβ基因片段的侧翼部分编码。这些基因片段的连接不精确，导致TCRβ链CDR3环长度和氨基酸组成存在显著变异性。与其他配对抗原受体链形成鲜明对比的是，TCRβ链和α链的CDR3环大小分布相对较窄且紧密匹配。因此，具有相对相似CDR3环大小的TCRα链和β链配对对于产生功能性αβTCR库可能很重要。在这里，我们表明，在胸腺细胞发育过程中，TCRβ链CDR3环大小分布受TCRβ链或αβTCR选择的影响最小。相反，这种分布主要在可变区基因组装水平上确定，并且关键取决于确保Dβ基因片段利用的V（D）J重组反应的独特特征。
