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Immunogenetics pp 635-680 | Cite as

Human Gm, Km, and Am Allotypes and Their Molecular Characterization: A Remarkable Demonstration of Polymorphism

  • Marie-Paule Lefranc
  • Gérard Lefranc
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 882)

Abstract

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.

Key words

IMGT Immunogenetics Allotype Haplotype Gm Km Am Gm-Am Immuno-informatics Immunoglobulin Antibody Allelic polymorphism IMGT-ONTOLOGY 

Notes

Acknowledgments

We thank Géraldine Folch for the “IMGT G3m allele butterfly” representation, Chantal Ginestoux and Saida Hadi-Saljoqi for their help, and François Ehrenmann for the 3D structure figures. We are very grateful to the IMGT® team for its expertise and constant motivation. This chapter is a tribute to Erna van Loghem, Liliane Rivat and Claude Ropartz.

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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.IMGT®, The International ImMunoGeneTics Information System®Université Montpellier 2, Laboratoire d’ImmunoGénétique Moléculaire (LIGM), Institut de Génétique Humaine (IGH), UPR CNRS1142MontpellierFrance

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