IMGT Collier de Perles: the New Look for IgSF and MhcSF in IMGT

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1 IMGT Collier de Perles: the New Look for IgSF and MhcSF in IMGT Quentin Kaas and Marie-Paule Lefranc Laboratoire d ImmunoGénétique Moléculaire Université Montpellier, UPR CNRS 1142, IGH Institut Universitaire de France 2nd Basic and Clinical Immunogenomics and 3rd Immunoinformatics (Immunomics) Conferences BCII 06, October 8-12, 2006, Budapest, Hungary The international ImMunoGeneTics information system Coordinator: M.-P. Lefranc, Montpellier, France

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3 IMGT : the adaptive immune response Vertebrate s Immunoglobulin (IG) T lymphocyte B lymphocyte peptide T cell receptor (TR) MHC Trimolecular complex Based on the IMGT-ONTOLOGY concepts (Lefranc M.-P. Immunome Res. 1, 3, 2005)

4 IMGT unique numbering V-DOMAIN (IG,TR) AND C-DOMAIN (IG,TR) AND V-LIKE-DOMAIN C-LIKE-DOMAIN (other than IG,TR) (other than IG,TR) Immunoglobulin superfamily (IgSF) G-DOMAIN (MHC) AND G-LIKE-DOMAIN (other than MHC) MHC superfamily (MhcSF)

5 V-DOMAIN and C-DOMAIN IgG1 The Immunoglobulin FactsBook, 2001

6 Immunoglobulin (IG) T cell receptor (TR) Contribution of the V-DOMAIN V-J-REGION Light chain 2 V-DOMAINs to the antigen binding site Alpha Gamma V-DOMAIN - Beta Delta V-D-J-REGION Heavy chain V-DJ-REGION V-J-REGION Membrane IgM T cell receptor The Immunoglobulin FactsBook, 2001

7 Immunoglobulin IgG IMGT Repertoire,

8 Immunoglobulin (IG) synthesis genomic DNA (IGH Locus 14q32) V D J C 3' 5 rearranged DNA 5 mrna 3' 2 x 1012 different IG per individual IMGT Repertoire,

9 Junctions of the V-DOMAINs VH V-KAPPA V-D-J junction V-J junction Side view Mouse(Mus musculus) E5.2Fv VH V-KAPPA View from above CDR3-IMGT= Complementarity determining region ( ) V-J junction ( ) V-D-J junction ( )

10 Generation of the JUNCTION diversity 3 V-REGION tgtgcgaaa ga N-REGION D-REGION tacc agcatattgtg gtggtgactgctat tcc N-REGION gatt JUNCTION C A P Y R G D T Y D Y S Wtgttgtgcgcca gcg cca tac cgg ggggtgactactat ggt gac act tat gat tac tcc tgg 5 J-REGION acaactggttcg actcctgg

11 Lefranc M.-P. et al. Dev. Comp. Immunol., 27, (2003)

12 IMGT contacts 41V - TRP (W) chain : 1u8k_B Tot NCo Pol HB NPol Cov SS Total number of atomic pair contacts Number of non covalent atomic Number of polar atomic pair contacts Number of hydrogen bonds Number of non polar atomic pair contacts Number of covalent links (other than chain covalent links) Number of disulfide bridges Kaas Q. et al. NAR 32, D208-D210 (2004)

13 V-DOMAIN The 3D structure of a V-DOMAIN (IG or TR) 9 antiparallel beta strands: A, B, C, C, C, D, E, F and G linked by beta turns: AB, CC, C D, DE and EF and loops: BC or CDR1-IMGT C C or CDR2-IMGT and FG or CDR3-IMGT forming a sandwich of two sheets [ABED][GFCC C ].

14 IMGT Collier de Perles on two layers Kaas Q. et al. NAR 32, D208-D210 (2004)

15 IMGT Web resources: pages HTML IMGT Collier de Perles IMGT Protein Display IMGT Alignment of alleles

16 IMGT tools for V-DOMAIN sequences: 1. IMGT/V-QUEST V-GENE JUNCTION J-GENE Giudicelli et al. Nucleic Acids Res. 32, W435-W440 (2004)

17 Giudicelli et al. Nucleic Acids Res. 32, W435-W440 (2004)

18 IMGT tools for V-DOMAIN sequences: 2. IMGT/JunctionAnalysis Addition Addition Mutation Délétion Délétion Délétion

19 The eleven IMGT amino acid classes according to the physico-chemical properties Pommié et al. J. Mol Recognit. 17, 17-32, 2004

20 r Pommié et al. J. Mol Recognit. 17, 17-32, 2004

21 Camelidae (camel, llama) antibodies gdna mrna Antibody IgG1 IgG2

22 IMGT Collier de Perles Camelus dromedarius (Camel) VH Single-Domain Antibody (1jto_A) CDR-IMGT lengths [8.8.26] 42: F, Y 49: E, Q 50: R, C 52: G, F, L, W

23 V-LIKE-DOMAIN Homo sapiens Myelin oligodendrocyte glycoprotein (MOG) CDR-IMGT lengths [9.6.9] N-glycosylated site N30 (BC loop) is conserved in Rattus norvegicus MOG which has been crystallized (1pkq). Duprat, E. et al., Recent Res. Develop. Human Genet., 2, (2004)

24 C-DOMAIN and C-LIKE-DOMAIN The 3D structure of a C-LIKE-DOMAIN (IgSF other than IG or TR) is similar to that of a C-DOMAIN (IG or TR) BC 7 antiparallel beta strands: A, B, C, D, E, F and G CD linked by beta turns: AB, DE and EF transversal strand: CD or loops: BC or CDR1-IMGT and FG or CDR3-IMGT FG forming a sandwich of two sheets [ABED][GFC] or [ABE][GFCD]

25 C-LIKE-DOMAIN FCGR3B The distinction between C1 and C2 becomes unnecessary as discussed in Dev. Comp. Immunol. 29, (2005). Bertrand G. et al., Tissue Antigens, 64, (2004)

26 MHCI MHC class I and MHC class II The groove is made by two G-DOMAINs that belong both to the same chain I-ALPHA in MHC class I each one to a different chain II-ALPHA and II-BETA in MHC class II

27 IMGT Colliers de Perles for G-DOMAIN IMGT pmhc contact sites: MHC class I (1ao7) Disulfide bridge C11-C74 61A and 72A Can be compared with the IMGT reference pmhc contact sites for pmhc-i with 9-aa peptides: 74 structures

28 1ao7

29 IMGT Colliers de Perles for G-DOMAIN IMGT pmhc contact sites: MHC class II (1j8h) Disulfide bridge C11-C74 61A, 61B and 72A (except for H2-AB) Can be compared with the IMGT reference pmhc contact sites for pmhc-ii and the 9 aa in the groove: 44 structures

30 1j8h

31 G-DOMAIN and G-LIKE-DOMAIN The 3D structure of a G-LIKE-DOMAIN (MhcSF other than MHC) is similar to that of a G-DOMAIN (MHC) AB CD D C B BC A BC A B C D AB CD 4 antiparallel beta strands: A, B, C, D linked by beta turns: AB, BC and CD («floor» of the groove or platform) one long helix («wall» of the groove)

32 G-LIKE-DOMAIN MICA G-ALPHA1LIKE [D1] G-ALPHA2LIKE [D2] [D3] Position 54A is characteristics of the G-ALPHA1-LIKE of MHC I-like Frigoul, A. et al., Recent Res. Develop. Human Genet., 3, (2005)

33 Interactions between domains (1e4k) IGHG1 (FC-GAMMA1) CH2 C-DOMAIN FCGR3 B [D2 ] C-LIKEDOMAIN [D1] C-LIKE-DOMAIN

34 IMGT-ONTOLOGY concepts: IMGT Scientific chart rules ImmunoGrid Partners CINECA, Bologna, Italy University of Queensland, Australia CNR, Italy CNRS, France Technical University of Denmark Birbeck College, UK University of Bologna, Italy University of Catania, Italy

35 The IMGT team at Montpellier

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37 IMGT pmhc contact sites H2-K1*01 8 residue peptide (code 1jtr) Lefranc et al. Dev. Comp. Immunol. 29, (2005)

38 IMGT pmhc contact sites H2-K1*01 (code 1jtr) 8 residue peptide Kaas and Lefranc In Silico Biology 2005