IMGT, the international ImMunoGeneTics database

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IMGT, the international ImMunoGeneTics database
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  © 2000 Oxford University Press Nucleic Acids Research, 2000, Vol. 28, No. 1  219–221 IMGT, the international ImMunoGeneTics database Manuel Ruiz, Véronique Giudicelli, Chantal Ginestoux, Peter Stoehr 1 , James Robinson 2 ,Julia Bodmer 2 , Steven G. E. Marsh 3 , Ronald Bontrop 4 , Marc Lemaitre 5 , Gérard Lefranc,Denys Chaume and Marie-Paule Lefranc* Laboratoire d’ImmunoGénétique Moléculaire, LIGM, UPR CNRS 1142 IGH, 141 rue de la Cardonille,34396 Montpellier Cedex 5, France,  1 EMBL Outstation EBI, Hinxton, UK,  2 ICRF, Oxford, UK,  3 ANRI, London, UK, 4 BPRC, Rijswijk, The Netherlands and  5 EUROGENTEC S.A., Seraing, Belgium Received September 29, 1999; Revised October 2, 1999; Accepted October 13, 1999 ABSTRACTIMGT, the international ImMunoGeneTics database( ), is a high-quality integrateddatabase specialising in Immunoglobulins (Ig), T cellReceptors (TcR) and Major HistocompatibilityComplex (MHC) molecules of all vertebrate species,created in 1989 by Marie-Paule Lefranc, UniversitéMontpellier II, CNRS, Montpellier, France (,IMGTincludestwodata-bases: IMGT/LIGM-DB, a comprehensive database ofIg and TcR from human and other vertebrates, withtranslation for fully annotated sequences, and IMGT/HLA-DB,adatabaseofthehumanMHCreferredtoasHLA (Human Leucocyte Antigens). The IMGT serverprovides a common access to expertized genomic,proteomic, structural and polymorphic data of Ig andTcR molecules of all vertebrates. By its high qualityand its easy data distribution, IMGT has importantimplications in medical research (repertoire inautoimmune diseases, AIDS, leukemias, lymphomas),therapeutic approaches (antibody engineering),genome diversity and genome evolution studies.IMGT is freely available at .The IMGT Index is provided at the IMGT Marie-Paulepage( IMGT, the international ImMunoGeneTics database (1), createdin 1989 by Marie-Paule Lefranc (Université Montpellier II,CNRS, Montpellier, France;, is a highquality integrated database specialising in Immunoglobulins (Ig),T cell Receptors (TcR) and Major Histocompatibility Complex(MHC) molecules of all vertebrate species (IMGT home pageat ).IMGT comprises expertly annotateddataandconsistsatpresentoftwodatabases:IMGT/LIGM-DB, acomprehensive database of Ig and TcR from human and othervertebrates, with translation for fully annotated sequences, andIMGT/HLA-DB, a database of the human MHC referred to asHLA (Human Leucocyte Antigens). IMGT distributes highquality data with an important increment value added by theIMGT expert annotations. IMGT is a unique immunogeneticsdatabase for the genome, proteome, structure and polymorphismdata of Ig, TcR and HLA. An ontology has been constructed byIMGT in order to provide controlled vocabulary and annotationrules which are indispensable to ensure accuracy, consistencyand coherence in IMGT (2). The IMGT Index is available atthe IMGT Marie-Paule page ( IMGTindex.html ). IMGT/LIGM-DB ORGANIZATION AND CONTENT IMGT/LIGM-DB development is mainly based on a relationalmodel organization. The database is maintained with SYBASEas relational DBSM (Data Base System Manager). IMGTclosely follows the content of Ig and TcR sequences fromgeneralist databases and currently contains more than 34 300nucleic acid sequences of Ig or TcR from 81vertebrate species,andtranslation forfully annotated sequences. IMGT sequencesare identified by the EMBL/GenBank/DDBJ (3–5) accession number. IMGT standardized keywords for Ig and TcR havebeen assigned to all entries. 177 feature labels are necessary todescribe all structural and functional subregions that composeIg and TcR sequences, whereas only seven of them are availablein EMBL, GenBank or DDBJ. Annotation of sequences withthese labels constitutes the main part of the expertize. AllIMGT/LIGM-DB information is available through searchcriteria described by Lefranc  et al.  (1). IMGT/HLA-DB ORGANIZATION AND CONTENT IMGT/HLA-DB is a specialist sequence database forsequences of the human major histocompatibility system. Itincludes the HLA sequences named by the WHO NomenclatureCommiteee for Factors of the HLA System. The databaseprovides users with online tools and facilities for the retrievaland analysis of HLA sequences. These include allele reports,alignment tools and a detailed database of all source cells. Theonline IMGT/HLA-DB submission tool allows the submissionof both new and confirmatory alleles to the WHO Committeefor Factors of the HLA system. The latest version (Release 1.4,October 1999) contains 1015 HLA alleles derived from overcomponent 2275 EMBL/GenBank/DDBJ sequences and sinceits release in December 1998 the IMGT/HLA-DB website hasreceived over 87 000 hits. The database currently focuses on *To whom correspondence should be addressed. Tel: +33 4 99 61 99 65; Fax: +33 4 99 61 99 01; Email:   220  Nucleic Acids Research, 2000, Vol. 28, No. 1 the human MHC but will be used as a model system to providea specialist database for the MHC sequences of other species. IMGT, AN INTEGRATED DATABASE Genome  IMGT reference sequences.  IMGT reference sequences for Igand TcR have been defined. They are listed in the germlinegene tables of the IMGT Repertoire (6–12). The IMGT reference directory is crucial for the high quality of IMGT/DNAPLOTresults (13,14).  IMGT gene name nomenclature.  The objective is to provideimmunologists and geneticists with a unique nomenclature perlocus which will allow extraction and comparison of data forthe complex B and T cell antigen receptor molecules, and theMHC, whatever the species. Proteome  IMGT unique numbering.  A uniform numbering system for Igand TcR sequences of all species has been established byMarie-Paule Lefranc to facilitate sequence comparison and cross-referencing between experiments from different laboratorieswhatever the antigen receptor (Ig or TcR), the chain type or thespecies (1,13,15,16). The IMGT unique numbering has allowed to redefine the limits of the framework (FR) andcomplementarity determiningregions (CDR)of the Ig and TcRvariable domain. Tables of FR-IMGT and CDR-IMGT lengthsare available from the IMGT Repertoire. Protein displays.  Protein displays are provided, in the IMGTRepertoire, for all the human germline variable regions of Ig andTcR (12) (Fig. 1), and in IMGT/HLA-DB for the human MHC. Polymorphic data  IMGT mutation and allele polymorphism description.  TheIMGT unique numbering has allowed a standardized IMGTdescription of mutations and the description of allele poly-morphisms and somatic hypermutations for the Ig and TcR.Alignments of alleles (13) and tables of alleles (7–11) have been set up for the coding region of the Ig and TcR germlinegenes (IMGT Repertoire) and for the human MHC genes(IMGT/HLA-DB). Probes and RFLP . A new section of the IMGT Repertoire,currentlydeveloped, contains data on probes used forthe analysisof Ig and TcR gene rearrangements and expressions, and RFLP(Restriction Fragment Length Polymorphism) studies. Structural data 2D representations (Colliers de Perles) and the IMGT/Colliersde Perles tool.  2D graphical representations designated asColliersde Perles(1,13)are providedforallthe humangermline variable regions of Ig and TcR (Fig. 1). The most recent 2D repre-sentations were generated with the IMGT/Colliers de Perles tool,developedbyGérardMennessier(LPM,Montpellier,France). 3D representations . In order to establish the first common dataaccess to all structural data concerning the Ig and TcR, structural Figure 1.  Examples of TcR V-REGION data in the IMGT Repertoire: protein display, 2D representation (Colliers de Perles) and 3D representation.   Nucleic Acids Research, 2000, Vol. 28, No. 1  221 data are retrieved from PDB (17,18) and from the literature. The IMGT unique numbering of the amino acids and theIMGT standardizationrules have beenapplied tothe PDB files.3DrepresentationsofIgandTcRV-REGIONsareavailable fromthe IMGT Repertoire. This visualization permits rapid correlationbetween protein sequences and 3D structure (Fig. 1). IMGT, A HIGH QUALITY DATABASE BASED ON THEIMGT-ONTOLOGY Ontology IMGT has developed a formal specification of the terms to beused in the domain of immunogenetics and bioinformatics.This has been the basis of the IMGT-ONTOLOGY (2), thefirst ontology in the domain, which allows the management of the immunogenetics knowledge for all vertebrate species. IMGT data coherence Control of coherence in IMGT combines data integrity controland biological data evaluation (19). IMGT INTEROPERABILITY AND DATA DISTRIBUTION Since July 1995, IMGT/LIGM-DB has been available on theweb at the IMGT home page. IMGT/HLA-DB is availablesince December 1998. IMGT provides the immunologists withan easy to use and friendly interface. IMGT has an exceptionalresponse with more than 12 000 requestsa week. From January1996 to October 1999, IMGT WWW server at Montpellier wasaccessedbymore than60000sites.IMGTdata are alsodistributedby EBI (distribution of CD-ROM, network and anonymous FTP server), by the CINESanonymous FTP server. IMGT is available from many SRSsites. To facilitate the integration of IMGT data intoapplications developed by other laboratories, we have built anApplication Programming Interface to access the database andits software tools (1,19). ELECTRONIC AND MAILING ADDRESSES IMGT home page: (IMGT ).IMGT page at EBI (flat file release and sequence submissioninformation): IMGT/LIGM-DB: (contacts , ).IMGT/HLA-DB: (contacts , , ).Anonymous FTP servers:, IMGT (contact ).IMGT Initiator and Coordinator: Marie-Paule Lefranc, IMGT,the International ImMunoGeneTics database, Laboratoired’ImmunoGénétique Moléculaire, LIGM, UPR CNRS 1142,IGH, rue de la Cardonille, 34396 Montpellier Cedex 5, France.Tel: +33 (0)4 99 61 99 65; Fax: +33 (0)4 99 61 99 01; CITING IMGT Authors who make use of the information provided by IMGTshould cite this article as a general reference for the access toand content of IMGT, and quote the IMGT home page URL, ACKNOWLEDGEMENTS We are deeply grateful to Gérard Mennessier (LIGMotif andIGMT/Colliers de Perles tools), Hans-Helmar Althaus andWerner Müller (DNAPLOT program), Johanne Abad,Sylvaine Artero, Valerie Barbié, Nathalie Bosc, ValérieContet, Géraldine Folch, Oksana Kravchuk, ChristèleMartinez, Violaine Moreau, Olga Posukh and DominiqueScaviner (IMGT/LIGM-DB), Natasja de Groot (IMGT/MHC).IMGT is funded by the European Union’s BIOTECHprogramme BIO4CT96-0037, the CNRS (Centre National dela Recherche Scientifique), and the MENRT (Ministère del’Education Nationale, de la Recherche et de la Technologie).Subventions have been received from the Imperial CancerResearch Fund, the National Institute of Health, NMDP(National Marrow Donor Program), the Anthony Nolan BoneMarrow Trust, ARC (Association pour la Recherche sur leCancer), ARP (Association de Recherche sur la Polyarthrite),FRM (Fondation pour la Recherche Médicale), LigueNationalecontreleCancer,andtheRégionLanguedoc-Roussillon. 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