Ebato M, Nitta T, Yagita H, Sato K, Okumura K
Department of Immunology and Neurosurgery, Juntendo University School of Medicine, Tokyo, Japan.
Eur J Immunol. 1994 Dec;24(12):2987-92. doi: 10.1002/eji.1830241210.
The purpose of this study was to assess the V-(D)-J junctional region of the T cell receptor (TCR), the CDR3 region, which is responsible for glioma-specific antigen contact in alpha beta TCR-mediated recognition. We sequenced the TCR alpha and beta chains of V alpha 7, and V beta 13.1 cDNA derived from tumor-infiltrating lymphocytes (TIL) of 12 glioma patients and also the corresponding clones from the patients' peripheral blood lymphocytes (PBL). A shared V beta 13.1 DJ sequence of the CDR3 region, ND beta N, was demonstrated in 49 of 66 V beta 13.1+ clones (74.2%) from the glioma TIL, whereas only 4 of 33 clones (12.1%) were observed in the V beta 13.1+ clones from the PBL (p < 0.001). A common VDJ sequence, FCASS (V beta 13.1)-YRLPWGTSDS (ND beta N)-GELFF (J beta 2.2), was observed not only in the gliomas from each patient, but also among all the patients with a preference for V beta 13.1. In contrast, the amino acid sequences of the V beta 13.1+ PBL clones were diverse and random. Next, we sequenced subclones from other V beta subfamilies randomly selected to compare their VDJ region rearrangements (V beta 3 and V beta 5.1). In contrast to V beta 13.1, the amino acid sequences of these junctional regions were completely different in these subclones. The V-J junctional region of the alpha chain is dominated by a few clones in some patients, and no shared amino acid sequences were detected in the TCR V alpha junctional region. However, in the N alpha region of the V alpha 7-bearing TIL clones, arginine was used in 27 of 44 clones (61.4%) compared to only 3 of 12 clones from the PBL (p < 0.05). These results are consistent with the hypothesis that a clonal expansion/accumulation of glioma lineage-specific T cells occurred in vivo at the tumor site and that these T cells may be recognizing glioma-specific antigens.
本研究的目的是评估T细胞受体（TCR）的V-(D)-J连接区，即负责在αβ TCR介导的识别中与胶质瘤特异性抗原接触的互补决定区3（CDR3）区域。我们对12例胶质瘤患者肿瘤浸润淋巴细胞（TIL）中Vα7和Vβ13.1 cDNA的TCRα和β链进行了测序，同时也对患者外周血淋巴细胞（PBL）中的相应克隆进行了测序。在来自胶质瘤TIL的66个Vβ13.1+克隆中的49个（74.2%）中发现了CDR3区域共享的Vβ13.1 DJ序列NDβN，而在来自PBL的Vβ13.1+克隆中仅观察到33个克隆中的4个（12.1%）（p<0.001）。不仅在每位患者的胶质瘤中，而且在所有患者中都观察到了一个常见的VDJ序列FCASS（Vβ13.1）-YRLPWGTSDS（NDβN）-GELFF（Jβ2.2），且偏好Vβ13.1。相比之下，Vβ13.1+ PBL克隆的氨基酸序列是多样且随机的。接下来，我们对随机选择的其他Vβ亚家族的亚克隆进行测序，以比较它们的VDJ区重排（Vβ3和Vβ5.1）。与Vβ13.1不同，这些连接区的氨基酸序列在这些亚克隆中完全不同。α链的V-J连接区在一些患者中由少数克隆主导，并且在TCR Vα连接区未检测到共享的氨基酸序列。然而，在携带Vα7的TIL克隆的Nα区域，44个克隆中的27个（61.4%）使用了精氨酸，而来自PBL的12个克隆中只有3个（p<0.05）。这些结果与以下假设一致，即胶质瘤谱系特异性T细胞在肿瘤部位发生了体内克隆扩增/积累，并且这些T细胞可能正在识别胶质瘤特异性抗原。
