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. 2014 Feb 5;5:22.
doi: 10.3389/fimmu.2014.00022. eCollection 2014.

Immunoglobulin and T Cell Receptor Genes: IMGT(®) and the Birth and Rise of Immunoinformatics

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Free PMC article

Immunoglobulin and T Cell Receptor Genes: IMGT(®) and the Birth and Rise of Immunoinformatics

Marie-Paule Lefranc. Front Immunol. .
Free PMC article

Abstract

IMGT(®), the international ImMunoGeneTics information system(®) (1), (CNRS and Université Montpellier 2) is the global reference in immunogenetics and immunoinformatics. By its creation in 1989, IMGT(®) marked the advent of immunoinformatics, which emerged at the interface between immunogenetics and bioinformatics. IMGT(®) is specialized in the immunoglobulins (IG) or antibodies, T cell receptors (TR), major histocompatibility (MH), and proteins of the IgSF and MhSF superfamilies. IMGT(®) has been built on the IMGT-ONTOLOGY axioms and concepts, which bridged the gap between genes, sequences, and three-dimensional (3D) structures. The concepts include the IMGT(®) standardized keywords (concepts of identification), IMGT(®) standardized labels (concepts of description), IMGT(®) standardized nomenclature (concepts of classification), IMGT unique numbering, and IMGT Colliers de Perles (concepts of numerotation). IMGT(®) comprises seven databases, 15,000 pages of web resources, and 17 tools, and provides a high-quality and integrated system for the analysis of the genomic and expressed IG and TR repertoire of the adaptive immune responses. Tools and databases are used in basic, veterinary, and medical research, in clinical applications (mutation analysis in leukemia and lymphoma) and in antibody engineering and humanization. They include, for example IMGT/V-QUEST and IMGT/JunctionAnalysis for nucleotide sequence analysis and their high-throughput version IMGT/HighV-QUEST for next-generation sequencing (500,000 sequences per batch), IMGT/DomainGapAlign for amino acid sequence analysis of IG and TR variable and constant domains and of MH groove domains, IMGT/3Dstructure-DB for 3D structures, contact analysis and paratope/epitope interactions of IG/antigen and TR/peptide-MH complexes and IMGT/mAb-DB interface for therapeutic antibodies and fusion proteins for immune applications (FPIA).

Keywords: IMGT; IMGT Collier de Perles; IMGT-ONTOLOGY; T cell receptor; immunogenetics; immunoglobulin; immunoinformatics; major histocompatibility.

Figures

Figure 1
Figure 1
An immunoglobulin (IG) or antibody. In vivo, an IG or antibody is anchored in the membrane of a B cell as part of a signaling B cell receptor (BcR = membrane IG+CD79) or, as shown here, is secreted (2). An IG is made of two identical heavy (H, for IG-HEAVY) chains and two identical light (L, for IG-LIGHT) chains (2). An IG comprises 12 domains (for example, IgG1, shown here) or 14 domains (IgM or IgE). The V-DOMAIN of each chain and the C-DOMAIN, one for each L chain and three for each H chain are highlighted. The light chain (here, L-KAPPA) is made of a variable domain (V-DOMAIN, here, V-KAPPA) at the N-terminal end and a constant domain (C-DOMAIN, here, C-KAPPA) at the C-terminal end. The heavy chain (here, H-GAMMA-1) is made of a VH (at the N-terminal end) and of three CH (four for H-MU or H-EPSILON) (Table 1) (2). The structure is that of the antibody b12, an IgG1-kappa, and so far the only complete human IG crystallized [1hzh from IMGT/3Dstructure-DB (http://www.imgt.org)].
Figure 2
Figure 2
A T cell receptor (TR)/peptide-major histocompatibility 1 (pMH1) complex. A TR (here, TR-alpha_beta) is shown (on top, upside down) in complex with an MH (here, MH1) presenting a peptide in its groove. In vivo, a TR is anchored in the membrane of a T cell as part of the signaling T cell receptor (TcR = TR+CD3). A TR is made of two chains, each comprising a variable domain (V-DOMAIN) at the N-terminal end and a constant domain (C-DOMAIN) at the C-terminal end (3). The domains are V-ALPHA and C-ALPHA for the TR-ALPHA chain, V-BETA and C-BETA for the TR-BETA chain (Table 2) (3). An MH1 is made of the I-ALPHA chain with two G-DOMAIN (G-ALPHA1 and G-ALPHA2) and a C-LIKE-DOMAIN (C-LIKE), non-covalently associated with the B2M (a C-LIKE-DOMAIN) (8). The TR/pMH1 complex structure is 3qfj from IMGT/3Dstructure-DB (http://www.imgt.org).
Figure 3
Figure 3
Variable (V) domain. An IG VH (V-DOMAIN) is shown as an example. (A) 3D structure ribbon representation with the IMGT strand and loop delimitations (64). (B) IMGT Collier de Perles on two layers with hydrogen bonds. The IMGT Collier de Perles on two layers show, in the forefront, the GFCC’C” strands (forming the sheet located at the interface VH/VL of the IG) and, in the back, the ABED strands. The IMGT Collier de Perles with hydrogen bonds (green lines online, only shown here for the GFCC′C″ sheet) is generated by the IMGT/Collier-de-Perles tool integrated in IMGT/3Dstructure-DB, from experimental 3D structure data (–13). (C) IMGT Collier de Perles on two layers generated from IMGT/DomainGapAlign (12, 27, 28). Pink circles (online) indicate amino acid (AA) changes compared to the closest genes and alleles from the IMGT reference directory. (D) IMGT Collier de Perles on one layer. AA are shown in the one-letter abbreviation. All proline (P) are shown online in yellow. IMGT anchors are in square. Hatched circles are IMGT gaps according to the IMGT unique numbering for V-domain (64, 66). Positions with bold (online red) letters indicate the four conserved positions that are common to a V-domain and to a C-domain: 23 (1st-CYS), 41 (CONSERVED-TRP), 89 (hydrophobic), 104 (2nd-CYS) (–66), and the fifth conserved position, 118 (J-TRP or J-PHE), which is specific to a V-DOMAIN and belongs to the motif F/W-G-X-G that characterizes the J-REGION (64, 66) (Table 4). The hydrophobic AA (hydropathy index with positive value: I, V, L, F, C, M, A) and tryptophan (W) (31) found at a given position in more than 50% of sequences are shown (online with a blue background color). Arrows indicate the direction of the beta strands and their designations in 3D structures. IMGT color menu for the CDR-IMGT of a V-DOMAIN indicates the type of rearrangement, V–D–J (for a VH here, red, orange, and purple) or V–J (for V-KAPPA or V-LAMBDA (not shown), blue, green, and greenblue) (2). The identifier of the chain to which the VH domain belongs is 1n0x_H (from the Homo sapiens b12 Fab) in IMGT/3Dstructure-DB (http://www.imgt.org). The CDR-IMGT lengths of this VH are [8.8.20] and the FR-IMGT are [25.17.38.11]. The 3D ribbon representation was obtained using PyMOL (http://www.pymol.org) and “IMGT numbering comparison” of 1n0x_H (VH) from IMGT/3Dstructure-DB (http://www.imgt.org).
Figure 4
Figure 4
Constant (C) domain. An IG CH (C-DOMAIN) is shown as an example. (A) 3D structure ribbon representation with the IMGT strand and loop delimitations (65). (B) IMGT Collier de Perles on two layers with hydrogen bonds. The IMGT Colliers de Perles on two layers show, in the forefront, the GFC strands and, in the back, the ABED strands (located at the interface CH1/CL of the IG), linked by the CD transverse strand. The IMGT Collier de Perles with hydrogen bonds (green lines online, only shown here for the GFC sheet) is generated by the IMGT/Collier-de-Perles tool integrated in IMGT/3Dstructure-DB, from experimental 3D structure data (–13). (C) IMGT Collier de Perles on two layers from IMGT/DomainGapAlign (12, 27, 28). (D) IMGT Colliers de Perles on one layer. Amino acids are shown in the one-letter abbreviation. All proline (P) are shown online in yellow. IMGT anchors are in square. Hatched circles are IMGT gaps according to the IMGT unique numbering for C-domain (65, 66). Positions with bold (online red) letters indicate the four conserved positions that are common to a V-domain and to a C-domain: 23 (1st-CYS), 41 (CONSERVED-TRP), 89 (hydrophobic), 104 (2nd-CYS) (–66) (Table 6), and position 118, which is only conserved in V-DOMAIN. The identifier of the chain to which the CH domain belongs is 1n0x_H (from the Homo sapiens b12 Fab, in IMGT/3Dstructure-DB, http://www.imgt.org). The 3D ribbon representation was obtained using PyMOL and “IMGT numbering comparison” of 1n0x_H (CH1) from IMGT/3Dstructure-DB (http://www.imgt.org).
Figure 5
Figure 5
Groove (G) domain. (A) 3D structure ribbon representation of the two G-domains. The two domains form a groove with a “floor” (four strands from each domain) and two “walls” (one helix from each domain) (8). The G-domains characterize the proteins of the MhSF, which comprises the MH (MH1 and MH2) and the RPI-MH1Like (MhSF other than MH) (8). The two G-DOMAIN of an MH1 are shown as an example. The view is from above the cleft with the G-ALPHA1 (on top) and G-ALPHA2 (on bottom). (B) IMGT Colliers de Perles of the two G-DOMAIN of an MH1. G-ALPHA1 (on top) and G-ALPHA2 (on bottom) belong to the I-ALPHA chain (8). (C) IMGT Colliers de Perles of the two G-DOMAIN of an MH2. G-ALPHA (on top) and G-BETA (on bottom) to the II-ALPHA chain and to the II-BETA chain, respectively (8). (D) IMGT Colliers de Perles of the two G-LIKE-DOMAIN of a RPI-MH1Like. G-ALPHA1-LIKE (on top) and G-ALPHA2-LIKE (on bottom) belong to the I-ALPHA-LIKE chain. Helices are moved outside of the floor to make it visible. Amino acids (AA) are shown in the one-letter abbreviation. All proline (P) are shown online in yellow. Hatched circles are IMGT gaps according to the IMGT unique numbering for G-domain (8, 66). The 3D ribbon representation was obtained using PyMOL and “IMGT numbering comparison” of 3qfj_A (G-ALPHA1 and G-ALPHA2) in IMGT/3Dstructure-DB (http://www.imgt.org). IMGT Colliers de Perles AA sequences are from 3qfj_A for MH1 (Homo sapiens HLA-A*0201), 1j8h_A and 1j8h_B for MH2 (Homo sapiens HLA-DRA*0101 and HLA-DRB1*0401, respectively) and 3huj_A for RPI-MH1Like (Homo sapiens CD1D). The IMGT Colliers de Perles were generated using the IMGT/Collier-de-Perles tool integrated in IMGT/3Dstructure-DB (http://www.imgt.org) (–13).
Figure 6
Figure 6
IMGT/3Dstructure-DB Domain pair contacts between VH and V-KAPPA and the ligand from an IG/Ag complex. The IG/Ag complex structure is 1n0x from IMGT/3Dstructure-DB (http://www.imgt.org) (–13). The ligand is a synthetic peptide. (A) Domain pair contacts between VH and the ligand. The Summary shows that there are a total of 106 atom pair contacts (10 polar including 1 hydrogen bond and 96 non-polar) for 17 pair contacts between the VH (1n0x_H) and the ligand (1n0x_P). Seven amino acids (AA) of the VH interact with the ligand. The list of the pair contacts show that three of them belong to the CDR2-IMGT (orange color online) and two of them to the CDR3-IMGT (purple color online), and together contribute to 81 atom pair contacts (including the hydrogen bond). The VH binds the ligand primarily by the N64 of the CDR2-IMGT and the P112.3 and Q112.2 of the CDR3-IMGT that are localized next to the top of the loops (Figure 3). The only two positions of the FR-IMGT that have contacts with the ligand are the anchors 55 and 66 of the CDR2-IMGT. In that structure, there is no contact of the CDR1-IMGT. (B) Domain pair contacts between V-KAPPA and the ligand. The Summary shows that there are a total of 195 atom pair contacts (32 polar including 3 hydrogen bonds and 163 non-polar) for 24 pair contacts between the V-KAPPA (1n0x_L) and the ligand (1n0x_P). Twelve AA of the VH interact with the ligand. The list of the pair contacts show that seven of them belong to the CDR1-IMGT (blue color online) and three of them to the CDR3-IMGT (greenblue color online) and together contribute to 174 atom pair contacts (including the three hydrogen bonds). The only two positions of the FR-IMGT that have contacts with the ligand are the positions 1 and 2 of the strand A of the FR1-IMGT. In that structure, there is no contact with the CDR2-IMGT.

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References

    1. Lefranc M-P, Giudicelli V, Ginestoux C, Jabado-Michaloud J, Folch G, Bellahcene F, et al. IMGT®, the international ImMunoGeneTics information system®. Nucleic Acids Res (2009) 37:D1006–1210.1093/nar/gkn838 - DOI - PMC - PubMed
    1. Lefranc M-P, Lefranc G. The Immunoglobulin FactsBook. London: Academic Press; (2001).
    1. Lefranc M-P, Lefranc G. The T Cell Receptor FactsBook. London: Academic Press; (2001).
    1. Lefranc M-P. Nomenclature of the human immunoglobulin genes. In: Coligan JE, Bierer BE, Margulies DE, Shevach EM, Strober W, editors. , editors. Current Protocols in Immunology. Hoboken NJ: John Wiley and Sons; (2000). p. A.11–137
    1. Lefranc M-P. Nomenclature of the human T cell receptor genes. In: Coligan JE, Bierer BE, Margulies DE, Shevach EM, Strober W, editors. , editors. Current Protocols in Immunology. Hoboken NJ: John Wiley and Sons; (2000). p. A.1O.1–A.10.23

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