Human Gm, Km, and Am allotypes and their molecular characterization: a remarkable demonstration of polymorphism.
Human Gm, Km, and Am allotypes and their molecular characterization: a remarkable demonstration of polymorphism.
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DOI：
10.1007/978-1-61779-842-9_34
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Lefranc, Gerard
中科院分区：
文献类型：
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作者：
Lefranc, Marie-Paule;Lefranc, Gerard
人免疫球蛋白同种异型是人免疫球蛋白（IG）重链和轻链上的抗原决定簇（或“标志物”），通常通过血凝抑制进行血清学测定。已在γ 1、γ 2、γ 3和α 2重链（分别命名为G1 m、G2 m、G3 m和A2 m同种异型）和κ轻链（Km同种异型）上鉴别出同种异型。Gm-Am同种异型以固定组合或Gm-Am单倍型遗传，这是由于人IGHC基因（14号染色体上IGH基因座中从5'至3'的IGHG 3、IGHG 1、IGHA 1、IGHG 2、IGHG 4、IGHE和IGHA 2）的连锁。Gm和Am同种异型已成为群体遗传学中最有力的工具之一，并且在人类IGHC基因的分子表征（基因转换、拷贝数变异、基因顺序）中非常有用。他们代表了一个主要的系统，了解免疫原性的多态性IG链，与氨基酸和构象变化。G3 m同种异型和氨基酸变化之间的相关性已经可能与IGHG 3基因的许多等位基因的测序，从不同人群的个体和已知的同种异型。在本章中，我们整合了遗传学和序列数据，并提供了一个更新的概述Gm-Am单倍型和Km同种异型。我们提出，第一次，一个完整的阐明G3 m同种异型，说明了“IMGT G3 m等位基因蝴蝶”的概念，允许图形表示的G3 m等位基因（一个基因的变体表达一组给定的同种异型）。同种异型的知识在抗体工程和单克隆抗体的人源化以改善免疫治疗中是重要的。
Human immunoglobulin allotypes are antigenic determinants (or "markers") determined serologically, classically by hemagglutination inhibition, on the human immunoglobulin (IG) heavy and light chains. The allotypes have been identified on the gamma1, gamma2, gamma3, and alpha2 heavy chains (they are designated as G1m, G2m, G3m, and A2m allotypes, respectively), and on the kappa light chain (Km allotypes). Gm-Am allotypes are inherited in fixed combinations, or Gm-Am haplotypes, owing to the linkage of the human IGHC genes (IGHG3, IGHG1, IGHA1, IGHG2, IGHG4, IGHE, and IGHA2 from 5' to 3' in the IGH locus on chromosome 14). Gm and Am allotypes have been one of the most powerful tools in population genetics and very instrumental in molecular characterization of the human IGHC genes (gene conversion, copy number variation, gene order). They represent a major system for understanding immunogenicity of the polymorphic IG chains, in relation with amino acid and conformational changes. The correlation between G3m allotypes and amino acid changes has been possible with the sequencing of many alleles of the IGHG3 gene, from individuals from different populations and with known allotypes. In this chapter, we integrate genetics and sequence data and provide an updated overview of the Gm-Am haplotypes and Km allotypes. We propose, for the first time, a complete elucidation of the G3m allotypes, illustrated by the "IMGT G3m allele butterfly" concept that allows a graphical representation of the G3m alleles (variants of a gene expressing a given set of allotypes). Knowledge of allotypes is important in antibody engineering and humanization of monoclonal antibodies to improve immunotherapy.