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）分析Melanomathe小鼠抗ID MAB MK2-23中的特殊型网络具有由抗HMW-MAA MAB 763.74.8HMW-MAA结合的抗原决定因素的内部形象8个抗anti-ID mAb在其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个抗Anti-ID mAb的精细特异性的多样性可能反映出其沉重和轻度链的可变区域的氨基酸序列中发生的少量体细胞突变，在对MAB MK2-23的免疫反应过程中。与组织底物的8个抗抗ID mAb的反应性模式相似，尽管不可叠加在用黑色素瘤细胞引起的抗HMW-MAA MAB 763.74的反应性模式。这种差异可能反映了抗ID MAB MK2-23的不完善的仿真抗原决定因素，抗HMW-MAA MAB MAB 763.744.与抗HMW-MAA MAB 763.74.80-95-195-195-195-100％的Anti-Anti-ID MAB的氨基酸序列相比其重和轻链的可变区域。在CDR1中发现了最高的同源性，在CDR3中最低。（2）抗ID MAB诱导延迟型型延迟型超敏反应。CELL介导的BALB/C小鼠中对培养的人黑色素瘤细胞COLO38的DTH反应是通过抗抗ID MAB 23和不相关的Isotype Mab 2-23和不相关的Isotype-Isype-Isype-Id-Id-ID-ID-ID-ID-ID-IDMAB TK6-74444444444-74-7444-7444-7444-744444。将注射到先前免疫的小鼠的右后垫和辐照的培养的人B淋巴样细胞LG-2的辐照Colo 38细胞被注入左侧作为对照。只有MK2-23可以诱导对HMW-MAA轴承人黑色素瘤细胞COLO38的反应。