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# IMGT, the international ImMunoGeneTics database

Marie-Paule Lefranc, Véronique Giudicelli, Chantal Ginestoux, Julia Bodmer, Werner Müller, Ronald Bontrop, Marc Lemaitre, Ansar Malik, Valérie Barbié, Denys Chaume

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## To cite this version:

Marie-Paule Lefranc, Véronique Giudicelli, Chantal Ginestoux, Julia Bodmer, Werner Müller, et al. IMGT, the international ImMunoGeneTics database. Nucleic Acids Research, 1999, 27 (1), pp.209-212. 10.1093/nar/27.1.209. hal-04090021

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https://hal.science/hal-04090021

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Distributed under a Creative Commons Attribution 4.0 International License
# IMGT, the international ImMunoGeneTics database

Marie-Paule Lefranc*, Véronique Giudicelli, Chantal Ginestoux, Julia Bodmer¹, Werner Müller², Ronald Bontrop³, Marc Lemaitre⁴, Ansar Malik⁵, Valérie Barbié and Denys Chaume⁶

Laboratoire d'ImmunoGénétique Moléculaire, Université Montpellier II, UPR CNRS 1142 IGH, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France, ¹ICRF, Oxford, UK, ²IFG, Köln, Germany, ³BPRC, Rijswijk, The Netherlands, ⁴EUROGENTEC S.A., Seraing, Belgium, ⁵EMBL Outstation EBI, Hinxton, UK and ⁶CNUSC, Montpellier, France

Received September 25, 1998; Revised and Accepted October 7, 1998

## ABSTRACT

IMGT, the international ImMunoGeneTics database (http://imgt.cnusc.fr:8104), is a high-quality integrated database specialising in Immunoglobulins (Ig), T cell Receptors (TcR) and Major Histocompatibility Complex (MHC) molecules of all vertebrate species, created in 1989 by Marie-Paule Lefranc, Université Montpellier II, CNRS, Montpellier, France (lefranc@ligm.igh.cnrs.fr). IMGT comprises three databases: LIGM-DB, a comprehensive database of Ig and TcR, MHC/HLA-DB, and PRIMER-DB (the last two in development); a tool, IMGT/DNAPLOT, developed for sequence analysis and alignments; and expertised data based on the IMGT scientific chart, the IMGT repertoire. By its high quality and its easy data distribution, IMGT has important implications in medical research (repertoire in autoimmune diseases, AIDS, leukemias, lymphomas), therapeutic approaches (antibody engineering), genome diversity and genome evolution studies. IMGT is freely available at http://imgt.cnusc.fr:8104

## INTRODUCTION

The international ImMunoGeneTics (IMGT) database (1), created in 1989 by Marie-Paule Lefranc (Université Montpellier II, CNRS, Montpellier, France; lefranc@ligm.igh.cnrs.fr), is a high quality integrated database specialising in Immunoglobulins (Ig), T cell Receptors (TcR) and Major Histocompatibility Complex (MHC) molecules of all vertebrate species (IMGT home page at http://imgt.cnusc.fr:8104). IMGT comprises alignment tables and expertly annotated sequences, and consists of three databases: (i) LIGM-DB, a comprehensive database of Ig and TcR from human and other vertebrates, (ii) MHC/HLA-DB, and (iii) PRIMER-DB (an Ig, TcR and MHC-related primer database), the two latter are currently being developed.

In order to provide the highest data quality, rules have been set up by LIGM, which constitute the IMGT scientific chart (2). Based on these rules, the IMGT repertoire has become the reference in immunogenetics, by providing expertised data such as Ig and TcR germline gene tables, alignments of alleles, protein

displays, Colliers de Perles, 3D representations, etc. IMGT scientific chart and IMGT repertoire are freely available at the IMGT Marie-Paule page from http://imgt.cnusc.fr:8104

IMGT/LIGM-DB proposes two new access media: the first one is a set of URLs to get direct links to the IMGT server, the second one is an IMGT/API that allows Java™ programmers to remotely access and integrate LIGM-DB data in other computer environments.

## IMGT/LIGM-DB ORGANIZATION AND CONTENT

LIGM-DB development is mainly based on a relational model organization. The database is maintained with SYBASE as relational DBSM (Data Base System Manager).

In September 1998, LIGM-DB contained 27 125 nucleic acid sequences of Ig or TcR from 81 species, and translation for fully annotated sequences. IMGT sequences are identified by the EMBL/GenBank/DDBJ (3–5) accession number. All LIGM-DB information is available through the following search criteria: catalogue, accession number, mnemonic, definition, length etc.; taxonomy, nucleic acid type, loci, genes or chains, functionality, structure, specificity, etc.; keywords; annotation labels; references. Selection is displayed at the top of the resulting sequences pages, so the users can check their own queries (Fig. 1). Users have the possibility to modify their request or consult the results (Fig. 1). They can (i) add new conditions to increase or decrease the number of resulting sequences, (ii) view details concerning the selected sequences and choose among eight possibilities: IMGT annotations, IGMT flat file, coding regions with protein translation, catalogue and external references, sequence in dump format, sequence in FASTA format, sequence with three reading frames, EMBL flat file, or (iii) search for sequence fragments corresponding to a particular label (Fig. 1).

## IMGT SCIENTIFIC CHART AND REPERTOIRE FOR DATA INTEGRITY AND IMGT QUALITY

### IMGT standardized keywords, labels and prototypes

IMGT standardized keywords for Ig and TcR have been assigned to all entries. 177 feature labels are necessary to describe all

<footnote>*To whom correspondence should be addressed. Tel: +33 4 99 61 99 65; Fax: +33 4 99 61 99 01; Email: lefranc@ligm.igh.cnrs.fr</footnote>
<figure><img src="image_4.png" /><figcaption>**Figure 1.** Example of a 'Results' screen from IMGT/LIGM-DB, http://imgt.cnusc.fr:8104. Note the search selection at the top of the page and the possibility, for the users, either to modify the request or to consult directly the results.</figcaption></figure>

structural and functional subregions that compose Ig and TcR sequences, whereas only seven of them are available in EMBL, GenBank or DDBJ. Annotation of sequences with these labels constitutes the main part of the expertise. Knowledge tables have been established to record and standardize theoretical and experimental research. Their content is under the responsibility of the IMGT coordinator.

Prototypes represent the organizational relationship between labels (6) and give information on the order and the expected length (in number of nucleotides) of the labels (7). Prototypes can apply to general configuration of Ig or TcR, independently of the chain type, the species or any other parameters like functionality. However, prototypes may also be established for very precise cases when sequence characteristics are clearly established (7).

## IMGT reference sequences

IMGT reference sequences have been defined based on one or, whenever possible, several of the following criteria: germline sequence, first sequence published, longest sequence, mapped

sequence. They are listed in the germline gene tables of the IMGT repertoire (8–10). IMGT reference sequences are crucial for the high quality of IMGT/DNAPLOT results (1,11), available from http://imgt.cnusc.fr:8104. The set of sequence fragments used for the IMGT/DNAPLOT tool can be downloaded in FASTA format from the IMGT repertoire at the IMGT Marie-Paule page from http://imgt.cnusc.fr:8104

## IMGT gene name nomenclature

The objective is to provide immunologists and geneticists with a unique nomenclature per locus which will allow extraction and comparison of data for the complex B and T cell antigen receptor molecules, whatever the species. IMGT nomenclature for Ig and TcR genes of all species follows the Human Gene Mapping Nomenclature rules. This has been applied as early as 1988, for the human IGL and IGH loci (12,13), and 1989 for all the genes of the human TRG locus (14,15). Correspondence between nomenclatures are described in tables. An exhaustive and
standardized list of human Ig and TcR gene names is available
from the IMGT repertoire at the IMGT Marie-Paule page.

## IMGT unique numbering

A uniform numbering system for Ig and TcR sequences of all
species has been established by Marie-Paule Lefranc to facilitate
sequence comparison and cross-referencing between experi-
ments from different laboratories whatever the antigene receptor
(Ig or TcR), the chain type or the species (1,16). In the IMGT
unique numbering, conserved amino acids from frameworks
(FR) always have the same number whatever the Ig or TcR
variable sequence, and whatever the species they come from. As
examples: cysteine 23 (in FR1), tryptophan 41 (in FR2), leucine
89 and cysteine 104 (in FR3). Correspondence between number-
ings is available at the IMGT Marie-Paule page.

## FR-IMGT and CDR-IMGT regions

The IMGT unique numbering has allowed to redefine the limits
of the framework (FR) and complementary determining regions
(CDR). The FR-IMGT and CDR-IMGT lengths become in
themselves crucial information which characterize variable
regions belonging to a group, a subgroup and/or a gene.
Framework amino acids (and codons) located at the same position
in different sequences can be compared without requiring
sequence alignments. This also holds for amino acids belonging
to CDR-IMGT of same length. Tables of FR-IMGT and
CDR-IMGT lengths are available from the IMGT repertoire
(http://imgt.cnusc.fr:8104).

## IMGT mutation and allele polymorphism description

The IMGT unique numbering has allowed a standardized IMGT
description of mutations and the description of allele polymorph-
isms and somatic hypermutations. These mutations and allelic
polymorphisms are described by comparison to the germline
IMGT reference sequence (allele *01). Based on these criteria,
alignments of alleles (1) and tables of alleles (8–10) have been set
up for the coding region of the germline genes and are available
from the IMGT repertoire.

## Protein displays, Colliers de Perles and 3D representations

Protein displays, and 2D graphical representations designated as
Colliers de Perles (1) are provided for all the human germline
variable regions of Ig and TcR, with FR-IMGT and CDR-IMGT
delimitations. Conserved hydrophobic amino acids are high-
lighted. The most recent 2D representations available at the
IMGT WWW interface from http://imgt.cnusc.fr:8104 were
generated with the IMGT/Colliers de Perles tool, developed by
Gérard Mennessier (LPM, Montpellier, France). Note that this
IMGT/Collier de Perles representation is also of great interest for
all sequences belonging to the V-set of the Ig superfamily
including non-rearranging sequences in vertebrates (Xenopus
CTXg1, human CD4, etc.) and in invertebrates (drosophila
amalgam, drosophila fasciclin II, etc.) (1,6). A standardization of
3D representations of Ig and TcR rearranged variable regions, in
which CDR loops are delimited according to the IMGT
numbering is being developed. Examples are available at the
IMGT Marie-Paule page.

# INNOVATIONS IN DATA COHERENCE AND DATA DISTRIBUTION

## IMGT data coherence

Control of coherence in IMGT combines data integrity control
and biological data evaluation (7).

*Data integrity control.* An administration system has been set up to coordinate the entry flow (7). This ensures coherence of the IMGT data which come from multiple sources: core data from EMBL, annotations from LIGM experts, and annotations from direct submissions by the authors.

*Biological data evaluation.* Knowledge tables have been built to record controled vocabulary and rules defined in the IMGT scientific chart (7). Knowledge tables allow (i) to control data coherence with the IMGT rules and prototypes, (ii) to identify potential sources of incoherences, (iii) to propose solutions in case of errors, and (iv) to take into account the evolution of knowledge issued from the immunogenetic research.

An ontology for Immunogenetics is currently built by IMGT in order to provide a semantic repository which will be of great help to increase interoperability between specialist and generalist databases.

## IMGT data distribution

Since July 1995, IMGT/LIGM-DB has been available on the
WWW server of CNUSC Montpellier at the IMGT home page
http://imgt.cnusc.fr: 8104 . IMGT provides the immunologists
with an easy to use and friendly interface.

From January 1996 to October 1998, IMGT WWW server at
Montpellier was accessed by more than 30 800 sites, with an
average of 5000-5500 requests a week. IMGT data are also
distributed by the CNUSC anonymous FTP server
(ftp://imgt.cnusc.fr/pub/IMGT), by EBI (distribution of CD-
ROM, network fileserver: netserv@ebi.ac.uk, and anonymous
FTP server: ftp.ebi.ac.uk). IMGT/LIGM-DB is available from
many SRS sites.

To facilitate the integration of IMGT data into applications
developed by other laboratories, we have built an Application
Programming Interface to access the database and its software
tools (7). This API includes: a set of URL links to access
biological knowledge data (keywords, labels, nomenclature,
etc.), a set of URL links to access all data related to one given
sequence. A set of Java™ class packages allows application
developers to select and retrieve data from an appropriate IMGT
server using an Object Oriented approach and the Java/RMI
protocol in a CORBA like architecture (7). The complete list of
information can be found at the IMGT informatics page from
http://imgt.cnusc.fr:8104

## ELECTRONIC AND MAILING ADDRESSES

IMGT home page: http://imgt.cnusc.fr:8104 (IMGT contact lefranc@ligm.igh.cnrs.fr).

Anonymous FTP servers: ftp://imgt.cnusc.fr/pub/IMGT (contact Denys.Chaume@cnusc.fr), ftp.ebi.ac.uk (contact malik@ebi.ac.uk).

IMGT Initiator and Coordinator: Marie-Paule Lefranc, IMGT,
the International ImMunoGeneTics database, Laboratoire
d'ImmunoGénétique Moléculaire, LIGM, UPR CNRS 1142,
IGH, 141 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;
Email: lefranc@ligm.igh.cnrs.fr

CITING IMGT

Authors who make use of the information provided by IMGT
should cite this article as a general reference for the access to and
content of IMGT, and quote the IMGT home page URL,
http://imgt.cnusc.fr:8104

ACKNOWLEDGEMENTS

We are deeply grateful to Gérard Lefranc for helpful discussion, Gérard Mennessier (LIGMotif and IGMT/Colliers de Perles), Hans-Helmar Althaus (DNAPLOT), Johanne Abad, Sylvaine Artero, Valérie Contet, Géraldine Folch, Christèle Martinez, Manuel Ruiz and Dominique Scaviner (LIGM-DB), James Robinson, Steven Marsh and Natasja de Groot (MHC/HLA-DB). IMGT is funded by the European Union's BIOTECH programme BIO4CT96-0037, the CNRS (Centre National de la Recherche Scientifique), and the MENRT (Ministère de l'Éducation Nationale, de la Recherche et de la Technologie). Subventions have been received from ARC (Association pour la Recherche sur le Cancer), ARP (Association de Recherche sur la Polyarthrite), FRM (Fondation pour la Recherche Médicale), Ligue Nationale contre le Cancer, and the Région Languedoc-Roussillon.

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