PSEUDOMONAS EXOTOXIN-ANTI-TAC - CELL-SPECIFIC IMMUNOTOXIN ACTIVE AGAINST CELLS EXPRESSING THE HUMAN T-CELL GROWTH-FACTOR RECEPTOR
PSEUDOMONAS EXOTOXIN-ANTI-TAC - CELL-SPECIFIC IMMUNOTOXIN ACTIVE AGAINST CELLS EXPRESSING THE HUMAN T-CELL GROWTH-FACTOR RECEPTOR
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DOI：
10.1172/jci111516
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发表时间：
1984-01-01
影响因子：
15.9
通讯作者：
PASTAN, I
中科院分区：
文献类型：
--
作者：
FITZGERALD, DJP;WALDMANN, TA;PASTAN, I
构建了一种免疫毒素，该免疫毒素根据T细胞生长因子（TCGF）受体在细胞表面的表达来区分2种T细胞系。将假单胞菌外毒素（PE）与识别人TCGF受体的单克隆抗体（anti-TAC）化学偶联制备了一种毒蛋白偶联物PE-anti-TAC。该偶联物对表达TCGF受体的细胞系HUT-102细胞有毒性，但对受体阴性细胞系MOLT-4细胞无毒。PE-anti-TAC的毒性在II型人腺病毒存在下增强了50倍，并通过添加过量的抗tac抗体降至对照水平。比较pe -抗转铁蛋白受体与pe -抗转铁蛋白受体对HUT-102细胞的毒性。为了比较EM对抗tac和抗tfr的进入途径，将辣根过氧化物酶（HRP）偶联到每个抗体上制成蛋白偶联物。抗tfr - hrp通过包被凹坑集中吸附内吞进入HUT-102细胞，大部分抗体以4度结合细胞表面。加热至37℃后10 min，受体体出现C。C. Anti-TAC-HRP也可通过包被坑和受体体进入HUT-102细胞；但是，与抗tfr相反，抗tac不能选择性地集中在包被的凹坑中，因此大多数这种表面结合的抗体在37度下10分钟内不能在HUT-102细胞中内化。C。
An immunotoxin was constructed with an activity that discriminated between 2 T cell lines based on the expression of the T cell growth factor (TCGF) receptor on their cell surface. A toxic protein conjugate, designated PE-anti-TAC, was made by chemically coupling pseudomonas exotoxin (PE) to a monoclonal antibody (anti-TAC) that recognizes the human TCGF receptor. This conjugate was toxic to HUT-102 cells, a cell line that expresses the TCGF receptor, but was nontoxic for MOLT-4 cells, a receptor-negative line. The toxicity of PE-anti-TAC was enhanced 50-fold in the presence of human adenovirus type II and was reduced to control levels by adding excess anti-TAC antibody. The toxicity of PE-anti-TAC for HUT-102 cells was compared with PE-anti-transferrin receptor. To compare the route of entry for both anti-TAC and anti-TFR using EM, protein conjugates were made by coupling horseradish peroxidase (HRP) to each antibody. Anti-TFR-HRP entered HUT-102 cells by concentrative adsorptive endocytosis via coated pits and the majority of the antibodies bound to the cell surface at 4.degree. C were seen in receptosomes by 10 min after warming to 37.degree. C. Anti-TAC-HRP was also found to enter HUT-102 cells via coated pits and receptosomes; but, in contrast to anti-TFR, anti-TAC did not selectively concentrate in coated pits and therefore the majority of this surface-bound antibody were not internalized in HUT-102 cells by 10 min at 37.degree. C.