ANALYSIS OF MELANOMA IDIOTYPE NETWORK AND IT'S CLINICAL APPLICATION

黑色素瘤独特型网络分析及其临床应用

基本信息

批准号：
05670735
负责人：
KAGESHITA Toshiro
金额：
$ 1.41万
依托单位：
KUMAMOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

(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.

(1) 黑色素瘤中独特型网络的分析小鼠抗 id 单克隆抗体 MK2-23 具有由抗 HMW-MAA 单克隆抗体 763.74.8HMW-MAA 结合抗抗 id 单克隆抗体所定义的抗原决定簇的内部图像，用单克隆抗体 MK2- 引发23 种特征在于它们与大量手术切除的良性和恶性黑素细胞肿瘤的反应性。 8 种抗抗 id 单克隆抗体在良性和恶性肿瘤的免疫过氧化物酶染色中显示出细微的差异。 8种抗抗id单克隆抗体精细特异性的多样性可能反映了单克隆抗体免疫应答过程中其重链和轻链可变区氨基酸序列中发生的少数体细胞突变MK2-23。 8 种抗抗 id mAb 与组织底物的反应模式相似，但不能与用黑色素瘤细胞引发的抗 HMW-MAA mAb 763.74 的反应模式重叠。这种差异可能反映出抗-id mAb MK2-23对抗-HMW-MAA mAb 763.74定义的抗原决定簇的不完美模拟。此外，将8种抗-抗-id mAb的氨基酸序列与抗-id mAb的氨基酸序列进行了比较。 HMW-MAA mAb 的可变区氨基酸序列具有 763.74.80-95% 和 85-100% 同源性分别是重链和轻链。 CDR1同源性最高，CDR3同源性最低。(2)抗id单克隆抗体诱导迟发型超敏反应。通过用抗id单克隆抗体免疫BALB/c小鼠，对培养的人黑色素瘤细胞Colo38进行细胞介导的DTH反应。 MK2-23 和不相关的同种型匹配的抗 id mAb TK6-74。将经照射的Colo 38细胞注射到先前免疫的小鼠的右后垫中，并将经照射的培养的人B淋巴样细胞LG-2注射到左侧作为对照。只有 MK2-23 可以诱导带有 HMW-MAA 的人黑色素瘤细胞 Colo38 的 DTH 反应。