Human immunoglobulin heavy-chain multigene deletions in healthy individuals

AbstractExtensive multigene deletions have been described in the human immunoglobulin heavy-chain constant region genes, some of them encompassing perhaps more than 100 kilobases. These deletions have all been observed in healthy individuals although these individuals lacked several immunoglobulin class or subclasses, being either homozygous for one deletion or heterozygous for two different deletions. The high frequency of consanguinity in the Tunisian population accounts for the high frequency of individuals displaying one or the orther of these deletions in a homozygous state

IMGT, the international ImMunoGeneTics information system(®): a standardized approach for immunogenetics and immunoinformatics

IMGT, the international ImMunoGeneTics information system(®), was created in 1989 by the Laboratoire d'ImmunoGénétique Moléculaire (LIGM) (Université Montpellier II and CNRS) at Montpellier, France. IMGT is a high quality integrated knowledge resource specialized in immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC) of human and other vertebrates, and related proteins of the immune system (RPI) of any species which belong to the immunoglobulin superfamily (IgSF) and to the MHC superfamily (MhcSF). IMGT consists of five databases, ten on-line tools and more than 8,000 HTML pages of Web resources. IMGT provides a common access to standardized data from genome, genetics, proteome and three-dimensional structures. The accuracy and the consistency of IMGT data are based on IMGT-ONTOLOGY, a semantic specification of terms to be used in immunogenetics and immunoinformatics. IMGT-ONTOLOGY comprises six main concepts: IDENTIFICATION, CLASSIFICATION, DESCRIPTION, NUMEROTATION, ORIENTATION and OBTENTION. Based on these concepts, the controlled vocabulary and the annotation rules necessary for the immunogenetics data identification, classification, description and numbering and for the management of IMGT knowledge are defined in the IMGT Scientific chart. IMGT is the international reference in immunogenetics and immunoinformatics for medical research (repertoire analysis of the IG antibody sites and of the TR recognition sites in autoimmune and infectious diseases, AIDS, leukemias, lymphomas, myelomas), veterinary research (IG and TR repertoires in farm and wild life species), genome diversity and genome evolution studies of the adaptive immune responses, biotechnology related to antibody engineering (single chain Fragment variable (scFv), phage displays, combinatorial libraries, chimeric, humanized and human antibodies), diagnostics (detection and follow up of residual diseases) and therapeutical approaches (grafts, immunotherapy, vaccinology). IMGT is freely available at

IMGT-ONTOLOGY 2012

Immunogenetics is the science that studies the genetics of the immune system and immune responses. Owing to the complexity and diversity of the immune repertoire, immunogenetics represents one of the greatest challenges for data interpretation: a large biological expertise, a considerable effort of standardization and the elaboration of an efficient system for the management of the related knowledge were required. IMGT®, the international ImMunoGeneTics information system® (http://www.imgt.org) has reached that goal through the building of a unique ontology, IMGT-ONTOLOGY, which represents the first ontology for the formal representation of knowledge in immunogenetics and immunoinformatics. IMGT-ONTOLOGY manages the immunogenetics knowledge through diverse facets that rely on the seven axioms of the Formal IMGT-ONTOLOGY or IMGT-Kaleidoscope: “IDENTIFICATION,” “DESCRIPTION,” “CLASSIFICATION,” “NUMEROTATION,” “LOCALIZATION,” “ORIENTATION,” and “OBTENTION.” The concepts of identification, description, classification, and numerotation generated from the axioms led to the elaboration of the IMGT® standards that constitute the IMGT Scientific chart: IMGT® standardized keywords (concepts of identification), IMGT® standardized labels (concepts of description), IMGT® standardized gene and allele nomenclature (concepts of classification) and IMGT unique numbering and IMGT Collier de Perles (concepts of numerotation). IMGT-ONTOLOGY has become the global reference in immunogenetics and immunoinformatics for the knowledge representation of immunoglobulins (IG) or antibodies, T cell receptors (TR), and major histocompatibility (MH) proteins of humans and other vertebrates, proteins of the immunoglobulin superfamily (IgSF) and MH superfamily (MhSF), related proteins of the immune system (RPI) of vertebrates and invertebrates, therapeutic monoclonal antibodies (mAbs), fusion proteins for immune applications (FPIA), and composite proteins for clinical applications (CPCA)

IMGT/GENE-DB: a comprehensive database for human and mouse immunoglobulin and T cell receptor genes

IMGT/GENE-DB is the comprehensive IMGT genome database for immunoglobulin (IG) and T cell receptor (TR) genes from human and mouse, and, in development, from other vertebrates. IMGT/GENE-DB is the international reference for the IG and TR gene nomenclature and works in close collaboration with the HUGO Nomenclature Committee, Mouse Genome Database and genome committees for other species. IMGT/GENE-DB allows a search of IG and TR genes by locus, group and subgroup, which are CLASSIFICATION concepts of IMGT-ONTOLOGY. Short cuts allow the retrieval gene information by gene name or clone name. Direct links with configurable URL give access to information usable by humans or programs. An IMGT/GENE-DB entry displays accurate gene data related to genome (gene localization), allelic polymorphisms (number of alleles, IMGT reference sequences, functionality, etc.) gene expression (known cDNAs), proteins and structures (Protein displays, IMGT Colliers de Perles). It provides internal links to the IMGT sequence databases and to the IMGT Repertoire Web resources, and external links to genome and generalist sequence databases. IMGT/GENE-DB manages the IMGT reference directory used by the IMGT tools for IG and TR gene and allele comparison and assignment, and by the IMGT databases for gene data annotation. IMGT/GENE-DB is freely available at http://imgt.cines.fr

Annotation and classification of the bovine T cell receptor delta genes

Abstract Background: gδ T cells differ from ab T cells with regard to the types of antigen with which their T cell receptors interact; gδ T cell antigens are not necessarily peptides nor are they presented on MHC. Cattle are considered a “gδ T cell high” species indicating they have an increased proportion of gδ T cells in circulation relative to that in “gδ T cell low” species such as humans and mice. Prior to the onset of the studies described here, there was limited information regarding the genes that code for the T cell receptor delta chains of this gδ T cell high species. Results: By annotating the bovine (Bos taurus) genome Btau_3.1 assembly the presence of 56 distinct T cell receptor delta (TRD) variable (V) genes were found, 52 of which belong to the TRDV1 subgroup and were comingled with the T cell receptor alpha variable (TRAV) genes. In addition, two genes belonging to the TRDV2 subgroup and single TRDV3 and TRDV4 genes were found. We confirmed the presence of five diversity (D) genes, three junctional (J) genes and a single constant (C) gene and describe the organization of the TRD locus. The TRDV4 gene is found downstream of the C gene and in an inverted orientation of transcription, consistent with its orthologs in humans and mice. cDNA evidence was assessed to validate expression of the variable genes and showed that one to five D genes could be incorporated into a single transcript. Finally, we grouped the bovine and ovine TRDV1 genes into sets based on their relatedness. Conclusions: The bovine genome contains a large and diverse repertoire of TRD genes when compared to the genomes of “gδ T cell low” species. This suggests that in cattle gδ T cells play a more important role in immune function since they would be predicted to bind a greater variety of antigens

From IMGT-ONTOLOGY to IMGT/LIGMotif: the IMGT® standardized approach for immunoglobulin and T cell receptor gene identification and description in large genomic sequences

<p>Abstract</p> <p>Background</p> <p>The antigen receptors, immunoglobulins (IG) and T cell receptors (TR), are specific molecular components of the adaptive immune response of vertebrates. Their genes are organized in the genome in several loci (7 in humans) that comprise different gene types: variable (V), diversity (D), joining (J) and constant (C) genes. Synthesis of the IG and TR proteins requires rearrangements of V and J, or V, D and J genes at the DNA level, followed by the splicing at the RNA level of the rearranged V-J and V-D-J genes to C genes. Owing to the particularities of IG and TR gene structures related to these molecular mechanisms, conventional bioinformatic software and tools are not adapted to the identification and description of IG and TR genes in large genomic sequences. In order to answer that need, IMGT^®, the international ImMunoGeneTics information system^®, has developed IMGT/LIGMotif, a tool for IG and TR gene annotation. This tool is based on standardized rules defined in IMGT-ONTOLOGY, the first ontology in immunogenetics and immunoinformatics.</p> <p>Results</p> <p>IMGT/LIGMotif currently annotates human and mouse IG and TR loci in large genomic sequences. The annotation includes gene identification and orientation on DNA strand, description of the V, D and J genes by assigning IMGT^®labels, gene functionality, and finally, gene delimitation and cluster assembly. IMGT/LIGMotif analyses sequences up to 2.5 megabase pairs and can analyse them in batch files.</p> <p>Conclusions</p> <p>IMGT/LIGMotif is currently used by the IMGT^®biocurators to annotate, in a first step, IG and TR genomic sequences of human and mouse in new haplotypes and those of closely related species, nonhuman primates and rat, respectively. In a next step, and following enrichment of its reference databases, IMGT/LIGMotif will be used to annotate IG and TR of more distantly related vertebrate species. IMGT/LIGMotif is available at <url>http://www.imgt.org/ligmotif/</url>.</p

A novel paradigm for cell and molecule interaction ontology: from the CMM model to IMGT-ONTOLOGY

International audienc

B Lymphocytes of Xeroderma Pigmentosum or Cockayne Syndrome Patients with Inherited Defects in Nucleotide Excision Repair Are Fully Capable of Somatic Hypermutation of Immunoglobulin Genes

Recent experiments have strongly suggested that the process of somatic mutation is linked to transcription initiation. It was postulated that a mutator factor loads onto the RNA polymerase and, during elongation, causes transcriptional arrest that activates DNA repair, thus occasionally causing errors in the DNA sequence. We report the analysis of the role of one of the known DNA repair systems, nucleotide excision repair (NER), in somatic mutation. Epstein–Barrvirus-transformed B cells from patients with defects in NER (XP-B, XP-D, XP-V, and CS-A) were studied. Their heavy and light chain genes show a high frequency of point mutations in the variable (V), but not in the constant (C) regions. This suggests that these B cells can undergo somatic hypermutation despite significant defects in NER. Thus, it is doubtful that NER is an essential part of the mechanism of somatic hypermutation of Ig genes. As an aside, NER seems also not involved in Ig gene switch recombination