Hawes G E, Struyk L, Godthelp B C, van den Elsen P J
Department of Immunohematology, University Hospital Leiden, The Netherlands.
J Immunol. 1995 Jan 15;154(2):555-66.
We have analyzed the TCR-alpha beta repertoire specific for a given peptide/MHC complex by using pairs of HLA-identical individuals ranging from monozygotic twins to unrelated individuals to examine the contribution of genetic background and HLA expression in shaping the potential response to a single antigenic epitope. This panel has been previously defined, demonstrating that the concordance of the peripheral TCR-alpha beta repertoires directly correlates to the level of relation and HLA identity. We have analyzed peptide-specific T cell clones derived from T cell lines from these individuals specific for MHC class II-restricted peptides: Mycobacterium bovis 65-kDa heat shock protein (65-kDa hsp) amino acids (aa) 3-13 (DR3-restricted), and myelin basic protein aa 84-102 (DR2-restricted). DNA sequence analysis was used to determine the composition of the TCR-alpha beta V regions. Although the overall TCR-alpha beta repertoires between individuals were diverse, an intra-individual limited restriction was evident. There was also a limited conservation in the response to the different peptides: high frequencies of V beta 2, 4, 7, 19, V alpha 21, and J alpha 17 responded to the MBP aa84-102, whereas these V/J regions were limited or absent in the 65-kDa hsp aa3-13 repertoire. Similarly, V beta 5.1 and J alpha 9 were increased in the 65-kDa hsp aa3-13 repertoire. Within the CDR3s, motifs could be identified that were similar between twins. Furthermore, one of these motifs resembled CDR3s previously found in corresponding animal models. Similarities could also be seen in the CDR3s of T cell clones sharing V gene usage and peptide specificity. Thus, the in vitro response to antigenic peptides seems to be quite heterogeneous overall and individual specific.
我们通过使用从同卵双胞胎到无关个体的 HLA 相同个体对，分析了针对给定肽/MHC 复合物的 TCR-αβ 库，以研究遗传背景和 HLA 表达在塑造对单一抗原表位潜在反应中的作用。该个体对面板先前已被定义，表明外周 TCR-αβ 库的一致性与亲缘关系程度和 HLA 同一性直接相关。我们分析了从这些个体的 T 细胞系中获得的肽特异性 T 细胞克隆，这些克隆针对 MHC II 类限制性肽：牛分枝杆菌 65-kDa 热休克蛋白（65-kDa hsp）氨基酸（aa）3-13（DR3 限制性）和髓鞘碱性蛋白 aa 84-102（DR2 限制性）。DNA 序列分析用于确定 TCR-αβ V 区的组成。尽管个体之间的总体 TCR-αβ 库是多样的，但个体内有限的限制性是明显的。对不同肽的反应中也存在有限的保守性：高频率的 Vβ2、4、7、19、Vα21 和 Jα17 对 MBP aa84-102 有反应，而这些 V/J 区域在 65-kDa hsp aa3-13 库中有限或不存在。同样，Vβ5.1 和 Jα9 在 65-kDa hsp aa3-13 库中增加。在 CDR3 内，可以识别出双胞胎之间相似的基序。此外，这些基序之一类似于先前在相应动物模型中发现的 CDR3。在共享 V 基因使用和肽特异性的 T 细胞克隆的 CDR3 中也可以看到相似性。因此，体外对抗原肽的反应总体上似乎相当异质且具有个体特异性。
