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与肺肿瘤相关抗原反应的人单克隆抗体22-13的核苷酸序列分析

Nucleotide sequence analysis of a human monoclonal antibody 22-13 reactive with lung tumor-associated antigen.

作者信息

Numasaki M, Nakamura K, Fukuoka Y, Sato N, Saeki H, Tachibana T, Hanai N, Nukiwa T, Kudo T

机构信息

Department of Respiratory Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan.

出版信息

Immunol Lett. 1998 Feb;60(2-3):111-20. doi: 10.1016/s0165-2478(97)00141-7.

DOI:10.1016/s0165-2478(97)00141-7
PMID:9557952
Abstract

A human monoclonal antibody (HuMAb) 22-13 (IgG1, kappa) recognizes a cytoplasmic antigen associated primarily with human lung tumors. This study reports the primary nucleotide and deduced amino acid sequences of the rearranged heavy and light chains of the HuMAb 22-13. This HuMAb uses a VH gene member of the V(H)Ia gene family, 51P1 and is productively rearranged with a D-D fusion product of the D(LR)2 and D(XP)2 germ line DH genes and the germ line JH3 gene. HuMAb 22-13 Vkappa belongs to the kappa light chain variable subgroup IIIb family and appears to be derived from the Humkv325 germ line gene and is rearranged with a germ line Jkappa5 gene. The results reveal that production of a HuMAb 22-13 is achieved by rearrangement of the 51P1/Humkv325 germ line variable region gene combination, associated with the autoimmune repertoire and that HuMAb 22-13 has a striking sequence homology to rheumatoid factors (RFs) of the Wa idiotypic family. HuMAb 22-13 and Wa RFs have in common V(H)Ia and VkappaIIIb gene segments, but use different DH, JH and Jkappa gene segments. However, in spite of this structural similarity, HuMAb 22-13 does not display rheumatoid factor activity. Taken together with the reported findings, these data indicate the representation of the shared usage of highly homologous variable region genes in entirely different humoral immune responses in the human system.

摘要

一种人源单克隆抗体(HuMAb)22 - 13(IgG1,κ链)识别一种主要与人肺肿瘤相关的细胞质抗原。本研究报告了HuMAb 22 - 13重链和轻链重排后的初级核苷酸序列及推导的氨基酸序列。该HuMAb使用V(H)Ia基因家族的VH基因成员51P1,并与种系DH基因D(LR)2和D(XP)2以及种系JH3基因的D - D融合产物进行有效重排。HuMAb 22 - 13的Vκ属于κ轻链可变亚组IIIb家族,似乎源自Humkv325种系基因,并与种系Jκ5基因重排。结果表明,HuMAb 22 - 13的产生是通过51P1/Humkv325种系可变区基因组合的重排实现的,这与自身免疫库相关,并且HuMAb 22 - 13与Wa独特型家族的类风湿因子(RFs)具有显著的序列同源性。HuMAb 22 - 13和Wa RFs共有V(H)Ia和VκIIIb基因片段,但使用不同的DH、JH和Jκ基因片段。然而,尽管存在这种结构相似性,HuMAb 22 - 13并不表现出类风湿因子活性。结合已报道的研究结果,这些数据表明在人类系统中完全不同的体液免疫反应中高度同源可变区基因的共享使用情况。

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