IMGT, the global reference in immunogenetics and immunoinformatics http://www.imgt.org Sofia Kossida IMGT Director Professor, Montpellier Universtity, IGH CNRS, Montpellier, France Marie-Paule Lefranc IMGT Founder and Director Emeritus Professor, Montpellier University, IGH CNRS, Montpellier, France February 10, 2015 Montpellier OMIS days http://www.imgt.o
IMGT, the global reference in immunogenetics and immunoinformatics Sofia Kossida IMGT Director Professor, Montpellier Universtity,
Jan 17, 2018
Immunoglobulin (IG) synthesis 2 x DIFFERENT ANTIBODIES 5'5'3'3' x POTENTIAL RECOMBINATIONS N-DIVERSITY SOMATIC MUTATIONS ABOUT POSSIBILITIES 3.5 x 10 5 ABOUT POSSIBILITIES 6.3 x FUNCTIONAL IG GENES 5' 3' VDJC x 23x x 5 Kappa x 4 -5 Lambda 5' 3' VJC HEAVY CHAIN LIGHT CHAIN IMGT Repertoire,
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IMGT, the global reference in immunogenetics and immunoinformatics
http://www.imgt.org
Sofia Kossida IMGT Director Professor, Montpellier Universtity, IGH CNRS, Montpellier, France
Marie-Paule Lefranc IMGT Founder and Director Emeritus Professor, Montpellier University, IGH CNRS, Montpellier, France
February 10, 2015Montpellier OMIS days
http://www.imgt.org
IMGT®: the adaptive immune response
Immunoglobulin (IG)
B lymphocyte T lymphocyte
T cell receptor (TR) MH
peptide
Trimolecular complex TR/pMH
Vertebrates http://www.imgt.org
Immunoglobulin (IG) synthesis
2 x 1012
DIFFERENT ANTIBODIES
5' 5'3' 3'x 1000
6300 POTENTIAL RECOMBINATIONS POTENTIAL RECOMBINATIONSN-DIVERSITY
SOMATIC MUTATIONS
ABOUT POSSIBILITIES3.5 x 105ABOUT POSSIBILITIES6.3 x 106
185 +165
150FUNCTIONAL IG GENES
5' 3'
V D J C
38- 46 x 23 x 6 30 - 35 x 5 Kappa 29- -33 x 4 -5 Lambda
5' 3'
V J CHEAVY CHAIN LIGHT CHAIN
IMGT Repertoire, http://www.imgt.org
http://imgt.cines.fr http://www.imgt.org
http://www.imgt.org
• 7 databases• 17 online tools• 15,000 web pages
• Sequences• Genes• Structures
• Immunoglobulins (IG) (or antibodies)• T cell receptors (TR)• MH• IgSF and MhSF
IMGTIMGT®®
created in 1989
IMGT-ONTOLOGY seven axioms:
To share, reuse and represent knowledge in Immunogenetics and Life Sciences
CLASSIFICATION
NUMEROTATION
DESCRIPTION
ORIENTATION
LOCALIZATION
Giudicelli and Lefranc, Bioinformatics (1999)
IDENTIFICATION OBTENTION
http://www.imgt.org
group
subgroup
allele
locus
is a member of an instance of
is a member of an instance of
is a variant of an instance of
is ordered in an instance of
IGLV
IGLV2
IGLV2-11
IGLV2-11*02
human IGL(22q11.2)
is ordered in
is a member of
is a variant of
is a member of
gene
« Concepts » « Instances »
http://www.imgt.org
Concepts of CLASSIFICATION
Concepts of CLASSIFICATION
1. group, subgroup, gene, allele
2. nomenclature for the V, D, J and C genes
3. immunoglobulin (IG) and T cell receptor (TR) genes
4. IMGT gene names approved by HUGO Nomenclature Committee (HGNC) in 1999.
5. IMGT alleles validated by WHO-IUIS/IMGT-NC
IMGT/GENE-DB: international reference database for IG and TR
genes (direct links from NCBI Gene) and alleles.
http://www.imgt.org
Concepts of DESCRIPTION
IMGT labels (capital letters)
http://www.imgt.org
IMGT Prototypes (table)
IMGT Scientific chart, http://www.imgt.org
Concepts of DESCRIPTION
1. standardized IMGT labels
2. used in all IMGT® databases and tools
•nucleotide and amino acid sequences (IMGT/LIGM-DB…)
•2D and 3D structures (IMGT/3Dstructure-DB…).
3. Sequence Ontology (SO) includes IMGT labels.
4. IMGT® databases can be queried using labels (a big ‘plus’ compared to generalist databases).
http://www.imgt.org
DESCRIPTION
IMGT/LIGM-DB
IMGT-ONTOLOGY:277 IMGT labels for sequences
285 IMGT labels for 3D structures
175 897 sequences from 346 species http://www.imgt.org
Lefranc et al. Dev. Comp. Immunol. 27, 55-77 (2003)
CDR-IMGT lengths [8.10.12]
1. IMGT unique numbering
2. IMGT Collier de Perles
(first one in 1997)
http://www.imgt.org
Concepts of NUMEROTATION
Lefranc et al. Dev. Comp. Immunol. 27, 55-77 (2003)
CDR-IMGT lengths [8.10.12]
- conserved AA (and codons) always at the same positions:
23 1st-CYS 41 CONSERVED-TRP 89 hydrophobic 104 2nd-CYS 118 J-PHE, J-TRP
- six anchors: delimitation of the FR-IMGT and CDR-IMGT
CDR-IMGT lengths are crucial information
http://www.imgt.org
Concepts of NUMEROTATION 1. IMGT unique numbering
2. IMGT Collier de Perles (first one in 1997)
View from above the CDR-IMGT Side view of the V-DOMAIN
V-J junctionV-D-J junction
V-DOMAIN: VH and V-KAPPA
CDR: complementarity determining regionCDR3-IMGT (105-117)V-D-J junction (104-118), V-J junction (104-118)
V-KAPPA VH
V-KAPPA
VH http://www.imgt.org
IMGT® http://www.imgt.org
JUNCTION
gatt tgtgcgaaa gtggtgactgctat actcctgg
3’V-REGION D-REGION 5’J-REGION
agcatattgtg acaactggttcg
Immunoglobulin V-D-J generation of sequence diversity
N-REGION
tcctacc
N-REGION
ga
C A P Y R G D T Y D Y S W tgtgcgcca ggggtgactactattgt gcg cca tac cgg ggt gac act tat gat tac tcc tgg
http://www.imgt.org
Yousfi Monod et al. Bioinformatics 20, i379-i385 (2004)
IMGT/JunctionAnalysis: analysis of the IG and TR junctions
http://www.imgt.org
The 11 IMGT physicochemical AA classes
Pommié et al. J. Mol Recognit. 17, 17-32 (2004)
http://www.imgt.org
IMGT/JunctionAnalysis
Yousfi Monod et al. Bioinformatics 20, i379-385 (2004)Pommié et al. J. Mol Recognit. 17, 17-32 (2004)
http://www.imgt.org
Analysis of the IG and TR junctions
V-REGIONidentity percent
IMGT/DomainGapAlign
http://www.imgt.org
IMGT Collier de Perles
AA that are different compared to the closest germline V and J genes and alleles
(e.g. for alemtuzumab: 11 AA in CDR1- and CDR2-IMGT and 14 AA in the FR-IMGT, compared to Homo sapiens IGHV4-59*01)
IMGT/DomainGapAlign: http://www.imgt.org
Towards «Potential immunogenicity evaluation»
Ehrenmann et al. Nucl. Acids Res. 38, D301-307 (2010)
IMGT/DomainGapAlign http://www.imgt.org
• very similar (+ + +)• similar (+ - +), (+ + -) • dissimilar (+ - -), (- + -), (- - +)• very dissimilar (- - -)
Towards «Potential immunogenicity evaluation»
Characteristics of the AA class changes:
Ehrenmann et al. Nucl. Acids Res. 38, D301-307 (2010)
(Hydropathy Volume Physicochemical) + : conserved classes - : different classes
IMGT/3Dstructure-DB http://www.imgt.org
IMGT/3Dstructure-DB
Hydrogen bonds
http://www.imgt.org
Lefranc et al. Nucl. Acids Res. 37, D1006-1012 (2009)
V-DOMAIN
Contacts VH-(Ligand), V-KAPPA-(Ligand) http://www.imgt.org
http://www.imgt.org
http://www.imgt.org
International Nonproprietary Name (INN)
Ehrenmann et al. Nucl. Acids Res. 38, D301-307 (2010)
IMGT/2Dstructure-DB
WHO-INN programme requires the CDR-IMGT lengths for antibodies.
http://www.imgt.org
Ehrenmann et al. Nucl. Acids Res. 38,D301-307 (2010)
IMGT/2Dstructure-DB
http://www.imgt.org
Ehrenmann et al. Nucl. Acids Res. 38, D301-307 (2010)
IMGT/2Dstructure-DB
DESCRIPTION
CLASSIFICATION
NUMEROTATION
Ehrenmann et al. Nucl. Acids Res. 38, D301-307 (2010)
IMGT/mAb-DB
Ehrenmann et al. Nucl. Acids Res. 38, D301-307 (2010)
Ehrenmann et al. Nucl. Acids Res. 38, D301-307 (2010)
Acknowledgements
BioSTIC-LR ACI IMPbio GIS AGENAE Plan Pluri-Formation Université Montpellier 2 ANR FLAVORES ANR BIOSYS GIS IBiSA Grand Plateau Technique Régional Languedoc-Roussillon GPTR «ImmunoGrid», 6th PCRDT, STREPS IST
http://www.imgt.org
and the companies that support the IMGT efforts of standardization.
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