ANALYSIS OF MELANOMA IDIOTYPE NETWORK AND IT'S CLINICAL APPLICATION

(1)黑色素瘤独特型网络分析小鼠抗-id mAb MK2-23具有抗hmw - maa mAb 763.74.8定义的抗原决定因子的内部图像。用mAb MK2-23诱导的hmw - maa结合的抗-id mAb对大量手术切除的良性和恶性黑色素细胞肿瘤具有反应性。8种抗-抗-单克隆抗体对良恶性肿瘤的免疫过氧化物酶染色均有细微差异。8种抗-抗-单克隆抗体精细特异性的多样性可能反映了在对mAb MK2-23的免疫应答过程中，其重链和轻链可变区氨基酸序列发生的体细胞突变较少。8种抗抗单克隆抗体与组织底物的反应模式相似，但与黑色素瘤细胞诱导的抗hmw - maa单克隆抗体763.74的反应模式不重叠。这种差异可能反映了抗hmw - maa mAb 763.74定义的抗原决定因子的抗id mAb MK2-23不完全模仿。8株抗-id单克隆抗体的氨基酸序列与抗hmw - maa单克隆抗体的氨基酸序列进行比较，其重链和轻链可变区氨基酸序列同源性分别为80-95%和85-100%。同源性最高的是CDR1，最低的是CDR3。(2)抗-id mAb诱导延迟型超敏反应。用抗单克隆抗体MK2-23和不相关的同型匹配的抗单克隆抗体TK6-74免疫BALB/c小鼠培养的人黑色素瘤细胞Colo38进行细胞介导的DTH反应。将经辐照的Colo 38细胞注射到免疫小鼠的右侧后垫，将经辐照培养的人B淋巴样细胞LG-2注射到左侧作为对照。只有MK2-23能诱导含有HMW-MAA的人黑色素瘤细胞Colo38发生DTH反应。

(1) Analysis of idiotype network in melanomaThe mouse anti-id mAb MK2-23 bears the internal image of the antigenic determinant defined by anti-HMW-MAA mAb 763.74.8HMW-MAA binding anti-anti-id Mabs elicited with mAb MK2-23 were characterized in their reactivity with a large panel of surgically removed benign and malignant melanocytic tumors. The 8 anti-anti-id mAbs displayd subtle differences in their immunoperoxidase staining of both benign and malignant tumors. The diversity in the fine specificity of the 8 anti-anti-id mAbs is likely to reflect the few somatic mutations which occur in the amino-acid sequence of the variable regions of their heavy and light chains in the course of the immune response to mAb MK2-23. The reactivity patterns of the 8 anti-anti-id mAbs with the tissue substrates are similar, although not superimposable upon that of the anti-HMW-MAA mAb 763.74 elicited with melanoma cells. This difference may reflect the imperfect mimicry by anti-id mAb MK2-23 of the antigenic determinant defined by anti-HMW-MAA mAb 763.74.Moreover the amino-acid sequences of 8 anti-anti-id mAbs were compared with that of anti-HMW-MAA mAb 763.74.80-95% and 85-100% homology were seen in the amino-acid sequence of the variable regions of their heavy and light chains, respectively. The highest homology was found in CDR1 and lowest in CDR3.(2) Induction of delayd type hypersensitivity by anti-id mAb.Cell mediated DTH reaction to cultured human melanoma cells Colo38 in BALB/c mice was done by immunized with anti-id mAb MK2-23 and unrelated isotype-matched anti-id mAb TK6-74. Irradiated Colo 38 cells injected into the right hind pad of the previously immunized mice and irradiated cultured human B lymphoid cells LG-2 were injected into the left side as control. Only MK2-23 could induce DTH reaction to HMW-MAA bearing human melanoma cells Colo38.