Diapositive 1

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Contribution of ImmunoGrid to standards and
concepts in immunology Marie-Paule
Lefranc IMGT, the international ImMunoGeneTics
information system CNRS,Montpellier,France Imm
unoGrid Third Annual Review Bruxelles, March13,
2009
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IMGT-ONTOLOGY
IMGT-ONTOLOGY seven axioms To share, reuse and
represent knowledge in Immunogenetics and Life
Sciences
OBTENTION
IDENTIFICATION
ORIENTATION
CLASSIFICATION
LOCALIZATION
DESCRIPTION
NUMEROTATION
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MHC1013 haplotypes
X
X
IG 2.1012 per individual
TR 2.1012 per individual
Immunoglobulin (IG) or antibody, T cell receptor
(TR) and MHC the key molecular components of the
adaptive immune response
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Immunoglobulin (IG) synthesis
Follow-up of immune repertoire in cancer
immunoprevention, cancer immunotherapy, vaccinatio
n, viral infection
Availability with the Next-Gen sequencers
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  CLASSIFICATION axiom
human IGL (22q11.2)
IGLV
group
locus
is a member of an instance of
is a member of
is ordered in an instance of
subgroup
IGLV2
is ordered in
is a member of an instance of
is a member of
gene
IGLV2-11
is a variant of an instance of
is a variant of
allele
IGLV2-1102
Concepts
Instances
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Contribution of ImmunoGrid to standards and
concepts of classification in immunology
International Standardized Nomenclature for IG
and TR

• HUGO Nomenclature Committee (HGNC)
• 2. Databases
• IMGT/GENE-DB 1 922 IG and TR genes and 2 942
  alleles
• UniProt addition of IG and TR reference
  sequences
• 3. Genome servers
• Entrez Gene (NCBI, USA) 2006-2009
• Ensembl (EBI, Hinxton UK) 2006-2009
• Vega (Sanger Institute, Hinxton UK) 2008-2009
• 4. WHO
• WHO/INN programme 2008-2009
• WHO/IUIS nomenclature committee 2008-2009

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DESCRIPTION axiom
PROTOTYPE for a V-GENE
V-GENE
V-EXON
L-PART1
FR3-IMGT
FR1-IMGT
FR2-IMGT
5 UTR
CDR3 -IMGT
3 UTR
V-REGION
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Standardized labels 241 for sequences 341 for 3D
structures
V-D-J-GENE 30 labels V-DOMAIN 18
labels JUNCTION 9 labels
10 relations (5x2)
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Contribution of ImmunoGrid to standards and
concepts of description in immunology
International Standardized Labels

• Standardized labels for
• IG,TR and other IgSF, MHC and other MhcSF.
• 2. Standardized labels for
• nucleotide and amino acid sequence, and 3D
  structure.
• 3. Standardized labels whatever
• the receptor type, the chain type, the species
• 4. Standardized description of the relations
• 5. Labels in Sequence Ontology (SO)

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V-DOMAIN
Human TR aß A6

TR V-ALPHA
TR V-BETA
1ao7_D
1ao7_E

CDR complementarity determining region
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Based on the IMGT unique numbering for V-DOMAIN
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IMGT Collier de Perles on 2 layers for V-DOMAIN
Based on the IMGT unique numbering for V-DOMAIN

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MHC-I chains and domains
MHC-I-ALPHA_B2M
(infected or tumoral cell)
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IMGT Colliers de Perles for G-DOMAIN
Based on the IMGT unique numbering for G-DOMAIN
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Contribution of ImmunoGrid to standards and
concepts of numerotation in immunology
International Standardized Numbering for domains

• IMGT unique numbering
• 2. IMGT Collier de Perles
• V type domain
• C type domain
• G type domain.
• 3. Bridge the gap between sequences and 3D
  structures
• whatever the receptor type (IG, TR and other
  IgSF MHC and other MhcSF) or the chain type.
• 4. Antibody humanization
• Immunogenicity evaluation
• FR-IMGT and CDR-IMGT delimitations
• Submissions to WHO/INN.

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TR/peptide/MHC complex
T cell receptor (TR)
Peptide
MHC- I
I-ALPHA
C
N
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Peptide unique numbering
Pocket F
Pocket A
Number of residues
Peptide sequence
8 amino acids 1jtr_Q
E - Q Y (K) F - -
Y S V
9 amino acids 1ao7_C
L - L F (G) Y - P
V Y V
MHC-I
10 amino acids 1bii_P
R - G P (G) R A F
V T I
IMGT pMHC contact sites
13 amino acids 1j8h_C
P K Y V K Q (N) T -
- L K L A T
MHC-II
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pMHC contact sites
G-ALPHA1 D1
G-ALPHA2 D2
D3
Human HLA-A0201 (MHC-I) and a 9-amino acid
peptide
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Residue_at_Position
TR
MHC
peptide
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Contribution of ImmunoGrid to standards and
concepts of interaction in immunology pMHC
contact analysis, Residue_at_Position

• 1. pMHC contact analysis
• 2. Residue_at_Position
• whatever the receptor type, chain type, domain
  type
• whatever the species.
• 3. Interactions of IG, TR and MHC and their
  complexes (IG/antigen, TR/pMHC).
• atom contact types
• atom contact categories
• 4. Standardized description of contact analysis
  between V, C and G domains

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Contribution of ImmunoGrid to standards and
concepts of interaction in immunology

• The concepts of classification, description,
• numerotation and interaction and the generated
• standards
• bridge the gap between sequences, structures
• and interactions for the key components of
• the adaptive immune response IG, TR and MHC
• and their complexes in the molecular models.
• 2. bridge the gap between molecular
• models in humans and in mice.