Use of IMGT Databases and Tools for Antibody Engineering and Humanization

IMGT^� , the international ImMunoGeneTics information system^� (http://www.imgt.org), was created in 1989 to manage the huge diversity of the antigen receptors, immunoglobulins (IG) or antibodies, and T cell receptors (TR). Standardized sequence and structure analysis of antibody using IMGT^� databases and tools allows one to bridge, for the first time, the gap between antibody sequences and three-dimensional (3D) structures. This is achieved through the IMGT Scientific chart rules, based on the IMGT-ONTOLOGY concepts of classification (IMGT gene and allele nomenclature), description (IMGT standardized labels), and numerotation (IMGT unique numbering and IMGT Colliers de Perles). IMGT^� is the international reference for immunogenetics and immunoinformatics and its standards are particularly useful for antibody humanization and evaluation of immunogenicity. IMGT^� databases for antibody nucleotide sequences and genes include IMGT/LIGM-DB and IMGT/GENE-DB, respectively, whereas nucleotide sequence analysis is performed by the IMGT/V-QUEST, IMGT/HighV-QUEST, and IMGT/JunctionAnalysis tools. In this chapter, we focus on IMGT^� databases and tools for amino acid sequences, two-dimensional (2D) and three-dimensional (3D) structures: the IMGT/DomainGapAlign and IMGT/Collier-de-Perles tools, the IMGT/2Dstructure-DB database for amino acid sequences of monoclonal antibodies (mAb, suffix -mab) and fusion proteins for immune applications (FPIA, suffix -cept) of the World Health Organization/International Nonproprietary Name (WHO/INN) programme and other proteins of interest, and the IMGT/3Dstructure-DB database for crystallized antibodies and its associated tools (IMGT/StructuralQuery, IMGT/DomainSuperimpose).