Kikuchi K, Okubo M, Sato T, Sato N
Department of Pathology, Sapporo Medical College, Japan.
Princess Takamatsu Symp. 1988;19:303-13.
The human autologous pair of a cytotoxic T cell clone and tumor line could be very useful for the investigation of the specific destruction of autologous tumor cells by cytotoxic T lymphocytes (CTL), including analysis for tumor-specific antigen possibly of the rejection type, clonotypic T cell antigen receptors and biochemical characteristics of the cytotoxic molecules produced from CTL. We established such a pair of autologous specific CTL clone TcHMC-1 and target clone HMC-1-8 that were derived from the metastatic pleural effusion of a patient with mammary carcinoma. TcHMC-1 showed more than 60% specific cytotoxicity against HMC-1-8, and it was confirmed, using cold target inhibition assays, that this clone did not demonstrate nonspecific cytotoxicity against a allogeneic targets as well as the natural killer (NK) cell activity. We also confirmed the in vivo action of TcHMC-1 against HMC-1-8 cells by the Winn assay in nude mice. Using anti-CD3, 4, and 8 as well as anti-class I monoclonal antibodies (mAbs), it was demonstrated that T cell antigen receptor molecule complexes Ti/T3 on TcHMC-1 and corresponding specific tumor antigens on HMC-1-8 are involved in the cytotoxicity under the restriction of major histocompatibility complex (MHC) class I products. We developed mAb 3A2 reacting with the specific antigens on HMC-1-8 that could play an important role in this autologous pair. This mAb inhibited selectively the cytotoxic action of TcHMC-1 against HMC-1-8, and identified a molecule with approximately 92 kd m.w. 3A2-defined antigen was highly expressed on autologous primary breast carcinoma tissue, but not on normal mammary gland in the same patient. Moreover, this antigen can be detected on approximately 50% of human allogeneic breast carcinomas, but not on other neoplastic cells except for 1 out of 10 prostatic carcinomas. It was also suggested that 3A2-defined antigen is not murine mammary tumor virus-related antigen.
细胞毒性T细胞克隆与肿瘤细胞系的人源自体配对，对于研究细胞毒性T淋巴细胞（CTL）对自体肿瘤细胞的特异性杀伤作用非常有用，包括分析可能具有排斥类型的肿瘤特异性抗原、克隆型T细胞抗原受体以及CTL产生的细胞毒性分子的生化特性。我们建立了这样一对源自乳腺癌患者转移性胸腔积液的自体特异性CTL克隆TcHMC-1和靶细胞克隆HMC-1-8。TcHMC-1对HMC-1-8显示出超过60%的特异性细胞毒性，并且通过冷靶抑制试验证实，该克隆对异基因靶细胞没有非特异性细胞毒性，也没有自然杀伤（NK）细胞活性。我们还通过裸鼠的Winn试验证实了TcHMC-1对HMC-1-8细胞的体内作用。使用抗CD3、4、8以及抗I类单克隆抗体（mAb），证明了TcHMC-1上的T细胞抗原受体分子复合物Ti/T3与HMC-1-8上相应的特异性肿瘤抗原在主要组织相容性复合体（MHC）I类产物的限制下参与了细胞毒性作用。我们开发了与HMC-1-8上的特异性抗原反应的mAb 3A2，其在这一自体配对中可能发挥重要作用。该mAb选择性地抑制了TcHMC-1对HMC-1-8的细胞毒性作用，并鉴定出一种分子量约为92 kd的分子。3A2定义的抗原在自体原发性乳腺癌组织上高度表达，但在同一患者的正常乳腺组织上不表达。此外，该抗原在约50%的人异体乳腺癌上可检测到，但在除10例前列腺癌中的1例以外的其他肿瘤细胞上未检测到。还表明3A2定义的抗原不是鼠乳腺肿瘤病毒相关抗原。
