IMGT Nomenclature and IMGT Unique Numbering: The Two Pillars of 35 Years of Immunoinformatics for Immunoglobulins (IG) or Antibodies and T Cell Receptors (TR).

IMGT®, the international ImMunoGeneTics information system® (IMGT) was created in 1989 by Marie-Paule Lefranc (Université de Montpellier and CNRS) at Montpellier (France) to manage the huge diversity of the antigen receptors, immunoglobulins (IG) or antibodies, and T cell receptors (TR) of the adaptive immune responses of the jawed vertebrates, from fish to human. The founding of IMGT marked the advent of immunoinformatics, a novel science that emerged at the interface between immunogenetics and bioinformatics. Immunoinformatics has been built starting from seven axioms which postulate that any object, any process and any relation has to be identified, described, classified, numbered, localized and orientated, and that the way it is obtained can be characterized. The IMGT-ONTOLOGY axioms (in capital letters) led to concepts from which IMGT Scientific chart rules were generated (e.g., CLASSIFICATION > concepts of classification > nomenclature, NUMEROTATION > concepts of numerotation > IMGT unique numbering …). The first IMGT immunoinformatics breakthrough was to make the variable (V), diversity (D), and joining (J) DNA, which participate in the synthesis of an IG or TR chain, officially recognized as "genes," as well as the conventional genes and to have them entered in the genomic databases. This led to the standardized IMGT nomenclature for IG and TR, based on locus, group, subgroup, gene and allele, with all the functional, open reading frame (ORF) and pseudogene human (Homo sapiens) IG and TR genes (including orphons) approved by HGNC in 1999. The second IMGT immunoinformatics breakthrough was to consider the variable and constant domains of the IG and TR as evolutionary related structural units (despite their fundamental differences in sequence (V-(D)-J region versus C-region exon, CDR-IMGT versus loops) and in number and type of strands ("9 antiparallel strands" versus "7 antiparallel strands and a transverse CD strand"). This led to the standardized IMGT unique numbering for V domain and for C domain (with four common amino acids, C23 and C104 of the disulfide bridge, W41, hydrophobic 89) and their IMGT Collier de Perles graphical representation. These breakthroughs have made the IMGT information system (7 databases, 17 tools, and over 25,000 Web pages) the global reference in immunogenetics and immunoinformatics for 35 years. The IMGT nomenclature bridges sequences and structures of engineered and humanized therapeutic antibodies and T cell receptors, and provides a standardized characterization of the alleles, allotypes and engineered variants of therapeutic monoclonal antibodies as published by the World Health Organization (WHO) International Nonproprietary Name (INN). The use of the IMGT unique numbering and IMGT Colliers de Perles for variable (V), constant (C) and groove (G) domains of the major histocompatibility (MH) allow to describe the specific amino acid interactions which characterize the antigen receptors of the adaptive immune system (paratope/epitope of the IG/antigen and of the TR/peptide-MH (pMH1 or pMH2). The standardization has been extended to the V-like, C-like, and G-like domains of proteins belonging to the immunoglobulin superfamily (IgSF) and MH superfamily (MhSF).