Search

IMGT®, the international ImMunoGeneTics information system®, http://www.imgt.org/, is at the forefront of the immunogenetics and immunoinformatics fields with more than 30 years of experience. IMGT® makes available databases and tools to the scientific community pertaining to the adaptive immune response, based on the IMGT-ONTOLOGY. We focus on the recent features of the IMGT® databases, tools, reference directories and web resources, within the three main axes of IMGT® research and development. Axis I consists in understanding the adaptive immune response, by deciphering the identification and characterization of the immunoglobulin (IG) and T cell receptor (TR) genes in jawed vertebrates. It is the starting point of the two other axes, namely the analysis and exploration of the expressed IG and TR repertoires based on comparison with IMGT reference directories in normal and pathological situations (Axis II) and the analysis of amino acid changes and functions of 2D and 3D structures of antibody and TR engineering (Axis III).

The adaptive immune system, along with the innate immune system, are the two main biological processes that protect an organism from pathogens. The adaptive immune system is characterized by the specificity and extreme diversity of its antigen receptors. These antigen receptors are the immunoglobulins (IG) or antibodies of the B cells and the T cell receptors (TR) of the T cells. The IG are proteins that have a dual role in immunity: they recognize antigens and trigger elimination mechanisms, to rid the body of foreign cells. The synthesis of the immunoglobulin heavy and light chains requires gene rearrangements at the DNA level in the IGH, IGK, and IGL loci. The rhesus monkey (

The bottlenose dolphin (Tursiops truncatus) belongs to the Cetartiodactyla and, similarly to other cetaceans, represents the most successful mammalian colonization of the aquatic environment. Here we report a genomic, evolutionary, and expression study of T. truncatus T cell receptor beta (TRB) genes. Although the organization of the dolphin TRB locus is similar to that of the other artiodactyl species, with three in tandem D-J-C clusters located at its 3′ end, its uniqueness is given by the reduction of the total length due essentially to the absence of duplications and to the deletions that have drastically reduced the number of the germline TRBV genes. We have analyzed the relevant mature transcripts from two subjects. The simultaneous availability of rearranged T cell receptor α (TRA) and TRB cDNA from the peripheral blood of one of the two specimens, and the human/dolphin amino acids multi-sequence alignments, allowed us to calculate the most likely interactions at the protein interface between the alpha/beta heterodimer in complex with major histocompatibility class I (MH1) protein. Interacting amino acids located in the complementarity-determining region according to IMGT numbering (CDR-IMGT) of the dolphin variable V-alpha and beta domains were identified. According to comparative modelization, the atom pair contact sites analysis between the human MH1 grove (G) domains and the T cell receptor (TR) V domains confirms conservation of the structure of the dolphin TR/pMH.

IMGT®, the international ImMunoGeneTics information system® is the global reference in immunogenetics and immunoinformatics. By its creation in 1989 by Marie-Paule Lefranc (Université de Montpellier and CNRS), IMGT® marked the advent of immunoinformatics, which emerged at the interface between immunogenetics and bioinformatics. IMGT® is specialized in the immunoglobulins (IG) or antibodies, T cell receptors (TR), major histocompatibility (MH), and proteins of the IgSF and MhSF superfamilies. T cell receptors are divided into two groups, αβ and γδ TR, which express distinct TR containing either α and β, or γ and δ chains, respectively. The TRβ locus (TRB) was recently described and annotated by IMGT® biocurators for several veterinary species, i.e., cat (Felis catus), dog (Canis lupus familiaris), ferret (Mustela putorius furo), pig (Sus scrofa), rabbit (Oryctolagus cuniculus), rhesus monkey (Macaca mulatta), and sheep (Ovis aries). The aim of the present study is to compare the genes of the TRB locus among these different veterinary species based on Homo sapiens. The results reveal that there are similarities but also differences including the number of genes by subgroup which may demonstrate duplications and/or deletions during evolution.

The adaptive immune response provides the vertebrate immune system with the ability to recognize and remember specific pathogens to generate immunity, and mount stronger attacks each time the pathogen is encountered. T cell receptors are the antigen receptors of the adaptive immune response expressed by T cells, which specifically recognize processed antigens, presented as peptides by the highly polymorphic major histocompatibility (MH) proteins. T cell receptors (TR) are divided into two groups, &alpha, &beta, and &gamma, &delta, which express distinct TR containing either &alpha, and &beta, or &gamma, and &delta, chains, respectively. The TR&alpha, locus (TRA) and TR&delta, locus (TRD) of bovine (Bos taurus) and the sheep (Ovis aries) have recently been described and annotated by IMGT&reg, biocurators. The aim of the present study is to present the results of the biocuration and to compare the genes of the TRA/TRD loci among these ruminant species based on the Homo sapiens repertoire. The comparative analysis shows similarities but also differences, including the fact that these two species have a TRA/TRD locus about three times larger than that of humans and therefore have many more genes which may demonstrate duplications and/or deletions during evolution.

IMGT®, the international ImMunoGeneTics information system® (http://www.imgt.org), is the global reference in immunogenetics and immunoinformatics. In 2019, for the first time, two pupils were welcomed within the team and introduced to immunoinformatics thank to the «Apprentis Chercheurs » programme founded by the association «l’Arbre des Connaissances ». This article describes the method and pedagogical approaches used, and demonstrates that immunoinformatics can be successfully taught to pupils of middle and high school.

IMGT(®), the international ImMunoGeneTics information system(®)(http://www.imgt.org) is the global reference in immunogenetics and immunoinformatics. By its creation in 1989 by Marie-Paule Lefranc (Université de Montpellier and CNRS), IMGT(®) marked the advent of immunoinformatics, which emerged at the interface between immunogenetics and bioinformatics. IMGT(®) is specialized in the immunoglobulins (IG) or antibodies, T cell receptors (TR), major histocompatibility (MH) and proteins of the IgSF and MhSF superfamilies. IMGT(®) is built on the IMGT-ONTOLOGY axioms and concepts, which bridged the gap between genes, sequences and 3D structures. The concepts include the IMGT(®) standardized keywords (identification), IMGT(®) standardized labels (description), IMGT(®) standardized nomenclature (classification), IMGT unique numbering and IMGT Colliers de Perles (numerotation). IMGT(®) comprises 7 databases, 17 online tools and 15,000 pages of web resources, and provides a high-quality and integrated system for analysis of the genomic and expressed IG and TR repertoire of the adaptive immune responses, including NGS high-throughput data. Tools and databases are used in basic, veterinary and medical research, in clinical applications (mutation analysis in leukemia and lymphoma) and in antibody engineering and humanization. The IMGT/mAb-DB interface was developed for therapeutic antibodies and fusion proteins for immunological applications (FPIA). IMGT(®) is freely available at http://www.imgt.org.

The international ImMunoGeneTics information system® (IMGT) (http://imgt.cines.fr), created in 1989, by the Laboratoire d'ImmunoGenetique Moleculaire LIGM (Universite Montpellier II and CNRS) at Montpellier, France, is a high-quality integrated knowledge resource specializing in the immunoglobulins (IGs), T cell receptors (TRs), major histocompatibility complex (MHC) of human and other vertebrates, and related proteins of the immune systems (RPI) that belong to the immunoglobulin superfamily (IgSF) and to the MHC superfamily (MhcSF). IMGT includes several sequence databases (IMGT/LIGM-DB, IMGT/PRIMER-DB, IMGT/PROTEIN-DB and IMGT/MHC-DB), one genome database (IMGT/GENE-DB) and one three-dimensional (3D) structure database (IMGT/3Dstructure-DB), Web resources comprising 8000 HTML pages (IMGT Marie-Paule page), and interactive tools. IMGT data are expertly annotated according to the rules of the IMGT Scientific chart, based on the IMGT-ONTOLOGY concepts. IMGT tools are particularly useful for the analysis of the IG and TR repertoires in normal physiological and pathological situations. IMGT is used in medical research (autoimmune diseases, infectious diseases, AIDS, leukemias, lymphomas, myelomas), veterinary research, biotechnology related to antibody engineering (phage displays, combinatorial libraries, chimeric, humanized and human antibodies), diagnostics (clonalities, detection and follow up of residual diseases) and therapeutical approaches (graft, immunotherapy and vaccinology). IMGT is freely available at http://imgt.cines.fr.

IMGT/LIGM-DB^1^ is the first and the largest IMGT^®^ database^2^ in which are managed, analysed and annotated more than 136,000 immunoglobulin (IG) and T cell receptor (TR) nucleotide sequences from human and 235 other vertebrate species (April 2009). The expert annotation of these sequences and the added standardized knowledge are based on IMGT-ONTOLOGY, the first ontology developed in the field of immunogenetics and immunoinformatics.^3^ The annotation of immunogenetic sequences requires important expertise, owing to the unusual structure (non-classical exon/intron structure) of the IG and TR genes and characteristic chain synthesis owing to DNA V-J and V-D-J rearrangements. The way to annotate these sequences depends on the molecular type (gDNA, mRNA, cDNA or protein) and the configuration type (germline or rearranged), and if sequences from the concerned species are present or not in the IMGT reference directory sets. IMGT/V-QUEST^5^ and internal tools (IMGT/Automat, IMGT/LIGMotif, IMGT/BLAST and IMGT/DomainGapAlign) were developed. The first step in annotation allows to identify the chain type (for instance IG-Heavy) and to assign standardized keywords (IDENTIFICATION axiom). The second step is the classification of IG and TR genes and alleles (CLASSIFICATION axiom). The third step is the description (DESCRIPTION axiom) of the V, D, J and C genes and alleles with specific standardized labels. There are more than 590 IMGT standardized labels from which 64 have been entered in Sequence Ontology (SO). The delimitation of the FR-IMGT and CDR-IMGT lengths and the positions of conserved amino acids based on the IMGT unique numbering (NUMEROTATION axiom) allow to bridge the gap between sequences and 3D structures.^6^ The complete annotation of immunogenetic germline (V, D, J) and C sequences is followed by the update of the IMGT Repertoire (IMGT Gene tables, Alignments of alleles, Protein displays, Colliers de Perles, etc.), IMGT® gene database (IMGT/GENE-DB) and IMGT reference directory sets of the IMGT® tools (IMGT/V-QUEST, IMGT/JunctionAnalysis and IMGT/DomainGapAlign).

The cDNA sequences of immunoglobulins (IG) and T cell receptors (TR) represent more than one half of the sequences in the IMGT^®^ nucleotide database IMGT/LIGM-DB^1^ and 75% of them are from human and mouse. A few cDNA are germline but the great majority results from a V-D-J or V-J gene rearrangement, spliced to a C gene. The IG and TR genes have been studied extensively in IMGT^®^ ("http://www.imgt.org":http://www.imgt.org) ^2^, which allowed to set up their nomenclature and the corresponding germline reference sequences. These standardized reference directory sets (one for each group of each locus) and the IMGT-ONTOLOGY axioms and derived concepts^3^ are the key elements indispensable to perform the annotation of IG and TR cDNA sequences. A Java program, IMGT/Automat^4^, was developed by IMGT^®^, to automatically annotate the IG and TR cDNA sequences and to produce a totally automatic and complete annotation. More than 9,000 human and mouse cDNA have already been successfully automatically annotated. The quality of the cDNA automatic annotation is equivalent to the quality of the annotation achieved by a human expert. The IMGT^®^ strategy is currently the only way, in the field of immunogenetics, to guarantee the annotation quality and the management of an always increasing number of IG and TR cDNA nucleotide sequences.

The immunoglobulin (IG) and T cell receptor (TR) major loci span about 6 Megabases (Mb) of the human genome on chromosomes 2, 7, 14 and 22, and 9 Mb in mouse on chromosomes 6, 12, 13, 14 and 16. There are seven major loci: three IG loci (IGH, IGK, IGL) and four TR loci (TRA, TRB, TRG, TRD), with a distinct repartition of the variable (V), diversity (D), joining (J) and constant (C) genes. The human genome comprises a total number of 608-665 IG and TR genes (371-422 IG and 237-243 TR), depending on the haplotypes, per haploid genome ^1, 2^ of which 531-588 genes are located in the major loci (distributed in 369-418 V, 32 D, 105-109 J and 25-29 C genes). There are also 77 orphons (68 IG and 9 TR) including two processed IG genes, outside the major loci. The number of functional IG and TR genes is 308-356 (136-171 IG and 172-185 TR) per haploid genome. The mouse genome comprises an approximate number of 876 IG and TR genes (624 IG and 252 TR). All these genomic data are available in the IMGT® gene database, IMGT/GENE-DB ^3^. The major contribution of IMGT/GENE-DB has been to establish, for the first time, a standardized nomenclature of the IG and TR genes and alleles of humans and other vertebrates. In April 2009, IMGT/GENE-DB manages 1999 genes and 3026 alleles. [1] Lefranc M.-P. and Lefranc G., The Immunoglobulin FactsBook, Academic Press, London, 458 pages (2001).[2] Lefranc M.-P. and Lefranc G., The T cell receptor FactsBook, Academic Press, London, 398 pages (2001).[3] Giudicelli V. et al. Nucleic Acids Res., 33, D256-261 (2005).

IMGT/LIGM-DB is the IMGT comprehensive database of immunoglobulin (IG) and T cell receptor (TR) nucleotide sequences from human and other vertebrate species. It was created in 1989 by LIGM, Montpellier, France and is the oldest and the largest database of IMGT. IMGT/LIGM-DB includes all germline (non-rearranged) and rearranged IG and TR genomic DNA (gDNA) and complementary DNA (cDNA) sequences published in generalist databases. IMGT/LIGM-DB allows searches from the Web interface according to biological and immunogenetic criteria through five distinct modules depending on the user interest. For a given entry, nine types of display are available including the IMGT flat file, the translation of the coding regions and the analysis by the IMGT/V-QUEST tool. IMGT/LIGM-DB distributes expertly annotated sequences. The annotations hugely enhance the quality and the accuracy of the distributed detailed information. They include the sequence identification, the gene and allele classification, the constitutive and specific motif description, the codon and amino acid numbering, and the sequence obtaining information, according to the main concepts of IMGT-ONTOLOGY. They represent the main source of IG and TR gene and allele knowledge stored in IMGT/GENE-DB and in the IMGT reference directory. IMGT/LIGM-DB is freely available at http://imgt.cines.fr.

IMGT, the international ImMunoGeneTics information system((R))(http://imgt.cines.fr) created in 1989, by the Laboratoire d'ImmunoGénétique Moléculaire (LIGM), Université Montpellier II and CNRS, Montpellier, France, is a high quality integrated information system, secialized in immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex of human and other vertebrates and related proteins of the immune system that belong to the IgSF and Mhc superfamilies. IMGT/LIGM-DB, the first and the largest IMGT database, manages more than 92,000 IG and TR nucleotide sequences from human and 150 other vertebrate species in May 2005. IMGT/LIGM-DB provides expertly annotated sequences and standardized knowledge based on IMGT-ONTOLOGY, the first ontology for immunogenetics and immunoinformatics. The strategy developed by IMGT, for the IG and TR nucleotide sequence annotation, involves two different approaches that depend on the nature of the sequences, genomic DNA (gDNA) or complementary DNA (cDNA).