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食蟹猴κ和γ免疫球蛋白cDNA的克隆与序列分析。

Cloning and sequence analysis of kappa and gamma cynomolgus monkey immunoglobulin cDNAs.

作者信息

Lewis A P, Barber K A, Cooper H J, Sims M J, Worden J, Crowe J S

机构信息

Department of Cell Biology, Wellcome Research Laboratories, Beckenham, Kent, U.K.

出版信息

Dev Comp Immunol. 1993 Nov-Dec;17(6):549-60. doi: 10.1016/s0145-305x(05)80010-2.

DOI:10.1016/s0145-305x(05)80010-2
PMID:8299853
Abstract

One gamma heavy chain and 10 kappa light chain cynomolgus monkey (Macaca fascicularis) immunoglobulin cDNAs have been cloned and sequenced. Comparisons of the variable (V) regions to human antibody sequences have revealed extensive identity, exhibiting 93% at the amino acid level for the VH framework regions, and 88-99% for the V kappa frameworks. Identification of very few cynomolgus monkey-specific framework region residues suggests a role for cynomolgus monkey antibodies as donators of variable regions to chimeric monoclonal antibodies for utilisation in human therapy with human constant (C) regions. The cynomolgus monkey C kappa region exhibited 83% amino acid identity to its human counterpart, and the C gamma region was 95, 93, 95, and 95% similar to the human C gamma 1, C gamma 2, C gamma 3, and C gamma 4 regions, respectively. Evolutionary analysis of the C gamma genes, using the silent molecular clock, suggests that the divergence between cynomolgus monkey and human occurred before the time at which the ancestral gamma gene diverged into the multiple isotypes observed in humans.

摘要

已克隆并测序了1条γ重链和10条κ轻链食蟹猴(猕猴)免疫球蛋白cDNA。可变(V)区与人抗体序列的比较显示出广泛的一致性,VH框架区在氨基酸水平上的一致性为93%,Vκ框架的一致性为88 - 99%。食蟹猴特异性框架区残基极少,这表明食蟹猴抗体可作为可变区供体,用于制备嵌合单克隆抗体,与人恒定(C)区一起用于人类治疗。食蟹猴Cκ区与其人类对应区域的氨基酸一致性为83%,Cγ区与人类Cγ1、Cγ2、Cγ3和Cγ4区的相似性分别为95%、93%、95%和95%。利用沉默分子钟对Cγ基因进行进化分析表明,食蟹猴和人类之间的分化发生在祖先γ基因分化为人类中观察到的多种同种型之前。

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