Yoshizawa K, Ota M, Kiyosawa K
Second Department of Internal Medicine, Shinshu University School of Medicine, Asahi, Matsumoto, Japan.
J Gastroenterol Hepatol. 1998 Jan;13(1):29-33. doi: 10.1111/j.1440-1746.1998.tb00541.x.
We established a cytotoxic T lymphocyte (CTL) clone directed against an autologous hepatocellular carcinoma (HCC) cell line SUHC-1 which had been established in our department from a patient with HCC associated with hepatitis C virus infection. The CTL clone lysed autologous SUHC-1 cells but did not lyse autologous Epstein-Barr (EB) virus-transformed B cells, natural killer (NK) cell-sensitive erythroleukaemia cell line K562, the NK-resistant B cell line Daudi, or allogeneic HCC cell lines, Hep-G2, Hep-3B, Mahlavu and PLC/PRF/5. The CTL clone expressed CD3 and CD8 molecules. The cytotoxic activity of the clone was inhibited by anti-CD3, anti-CD8 and anti-histocompatibility antigen (HLA) class I monoclonal antibodies. These results indicated that the CTL clone recognized HCC tumour antigen in an HLA class I-restricted manner. Furthermore, we investigated the T cell receptor (TCR) gene usage of the CTL clone. The CTL clone expressed TCR alphabeta. We searched for expression of TCR variable (V) alpha and beta regions and sequenced complementary determining region (CDR) 3 of the clone. The clone expressed V alpha14, junctional (J) region alpha9.7 and V beta7, J beta2.1. The amino acid sequence of the N region of the of chain was S-P-G-G-G-G-A-D-G-L-T and of the N-D-N region of the beta chain was S-W-T-G-A-S-T-D-T-Q-Y. These results suggested that HLA class I-restricted CTL play an important role in the elimination of human HCC cells.
我们建立了一个针对自体肝癌(HCC)细胞系SUHC-1的细胞毒性T淋巴细胞(CTL)克隆,该细胞系是我们科室从一名丙型肝炎病毒感染相关的肝癌患者中建立的。该CTL克隆可裂解自体SUHC-1细胞,但不能裂解自体爱泼斯坦-巴尔(EB)病毒转化的B细胞、自然杀伤(NK)细胞敏感的红白血病细胞系K562、NK抗性B细胞系Daudi或同种异体肝癌细胞系Hep-G2、Hep-3B、Mahlavu和PLC/PRF/5。该CTL克隆表达CD3和CD8分子。该克隆的细胞毒性活性受到抗CD3、抗CD8和抗组织相容性抗原(HLA)I类单克隆抗体的抑制。这些结果表明,该CTL克隆以HLA I类限制的方式识别肝癌肿瘤抗原。此外,我们研究了该CTL克隆的T细胞受体(TCR)基因使用情况。该CTL克隆表达TCRαβ。我们搜索了TCR可变(V)α和β区域的表达,并对该克隆的互补决定区(CDR)3进行了测序。该克隆表达Vα14、连接(J)区α9.7和Vβ7、Jβ2.1。α链N区的氨基酸序列为S-P-G-G-G-G-A-D-G-L-T,β链N-D-N区的氨基酸序列为S-W-T-G-A-S-T-D-T-Q-Y。这些结果表明,HLA I类限制的CTL在消除人肝癌细胞中起重要作用。