Lefranc Marie-Paule, Lefranc Gérard
IMGT®, The International ImMunoGeneTics Information System®, Université Montpellier 2, Laboratoire d'ImmunoGénétique Moléculaire (LIGM), Institut de Génétique Humaine (IGH), UPR CNRS1142, Montpellier, France.
Methods Mol Biol. 2012;882:635-80. doi: 10.1007/978-1-61779-842-9_34.
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.
人类免疫球蛋白同种异型是通过血清学方法确定的抗原决定簇（或“标记”），传统上通过血凝抑制法在人类免疫球蛋白（IG）重链和轻链上进行鉴定。已在γ1、γ2、γ3和α2重链上鉴定出同种异型（它们分别被指定为G1m、G2m、G3m和A2m同种异型），以及κ轻链上的同种异型（Km同种异型）。由于人类IGHC基因（位于14号染色体上IGH基因座中从5'到3'的IGHG3、IGHG1、IGHA1、IGHG2、IGHG4、IGHE和IGHA2）的连锁，Gm-Am同种异型以固定组合或Gm-Am单倍型的形式遗传。Gm和Am同种异型一直是群体遗传学中最强大的工具之一，对人类IGHC基因的分子特征（基因转换、拷贝数变异、基因顺序）非常有帮助。它们代表了一个主要系统，用于理解多态性IG链的免疫原性与氨基酸和构象变化的关系。通过对来自不同群体且具有已知同种异型的个体的IGHG3基因的多个等位基因进行测序，已实现G3m同种异型与氨基酸变化之间的相关性研究。在本章中，我们整合了遗传学和序列数据，并提供了Gm-Am单倍型和Km同种异型的最新概述。我们首次提出对G3m同种异型的完整阐释，并以“IMGT G3m等位基因蝴蝶”概念进行说明，该概念允许以图形方式表示G3m等位基因（表达给定一组同种异型的基因变体）。同种异型的知识在抗体工程和单克隆抗体人源化以改善免疫治疗方面很重要。
