TRDV

Immunoglobulins: 25 Years of Immunoinformatics and IMGT-ONTOLOGY

“…The founding of IMGT ® marked the advent of immunoinformatics, a new science, which emerged at the interface between immunogenetics and bioinformatics. For the first time, immunoglobulin (IG) or antibody and T cell receptor (TR) variable (V), diversity (D), joining (J) and constant (C) genes were officially recognized as “genes” as well as the conventional genes [ 3 , 4 , 5 , 6 ]. This major breakthrough allowed genes and data of the complex and highly diversified adaptive immune responses to be managed in genomic databases and tools.…”

“…It is characterized by a remarkable immune specificity and memory, which are properties of the B and T cells owing to an extreme diversity of their antigen receptors. The specific antigen receptors comprise the IG or antibodies of the B cells and plasmacytes [ 3 ], and the TR [ 4 ]. The IG recognize antigens in their native (unprocessed) form, whereas the TR recognize processed antigens, which are presented as peptides by the highly polymorphic major histocompatibility (MH, in humans HLA for human leucocyte antigens) proteins.…”

“…The potential antigen receptor repertoire of each individual is estimated to comprise about 2 × 10 12 different IG and TR, and the limiting factor is only the number of B and T cells that an organism is genetically programmed to produce [ 3 , 4 ]. This huge diversity results from the complex molecular synthesis of the IG and TR chains and, more particularly, of their variable domains (V-DOMAIN) which, at their N-terminal end, recognize and bind the antigens [ 3 , 4 ].…”

“…The potential antigen receptor repertoire of each individual is estimated to comprise about 2 × 10 12 different IG and TR, and the limiting factor is only the number of B and T cells that an organism is genetically programmed to produce [ 3 , 4 ]. This huge diversity results from the complex molecular synthesis of the IG and TR chains and, more particularly, of their variable domains (V-DOMAIN) which, at their N-terminal end, recognize and bind the antigens [ 3 , 4 ]. The IG and TR synthesis includes several unique mechanisms that occur at the DNA level: combinatorial rearrangements of the V, D and J genes that code the V-DOMAIN (the V-(D)-J being spliced to the C gene that encodes the C-REGION in the transcript); exonuclease trimming at the ends of the V, D and J genes; and random addition of nucleotides by the terminal deoxynucleotidyl transferase (TdT) that creates the junctional N-diversity regions, and later during B cell differentiation, for the IG, somatic hypermutations, gene conversion (e.g., in birds), and class or subclass switch in higher vertebrates [ 3 , 4 ].…”

“…The IMGT ® IG and TR gene names [ 3 , 4 , 5 , 6 ] were approved by the Human Genome Organisation (HUGO) Nomenclature Committee (HGNC) in 1999 [ 88 , 89 ] and were endorsed by the WHO-IUIS Nomenclature Subcommittee for IG and TR [ 46 , 47 ]. The IMGT ® IG and TR gene names are the official international reference and, as such, have been entered in IMGT/GENE-DB [ 8 ], in the Genome Database (GDB) [ 90 ], in LocusLink at the National Center for Biotechnology Information (NCBI) USA [ 91 ], in Entrez Gene (NCBI) when this database (now designated as “Gene”) superseded LocusLink [ 92 ], in NCBI MapViewer, in Ensembl at the European Bioinformatics Institute (EBI) [ 93 ], and in the Vertebrate Genome Annotation (Vega) Browser [ 94 ] at the Wellcome Trust Sanger Institute (UK).…”