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IMGT Standardization for Molecular Characterization of the T-cell Receptor/Peptide/MHC Complexes

  • Quentin Kaas
  • Elodie Duprat
  • Guillaume Tourneur
  • Marie-Paule Lefranc

Abstract

One of the key elements in the adaptive immune response is the presentation of peptides by the major histocompatibility complex (MHC) to the T-cell receptors (TR) at the surface of T cells. The characterization of the TR/peptide/MHC trimolecular complexes (TR/pMHC) is crucial to the fields of immunology, vaccination, and immunotherapy. In order to facilitate data comparison and cross-referencing between experiments from different laboratories whatever the receptor, the chain type, the domain, or the species, IMGT®, the international ImMunoGeneTics information system® (http://imgt.cines.fr), has developed IMGT-ONTOLOGY, the first ontology in immunogenetics and immunoinformatics. In IMGT/3Dstructure-DB, the IMGT three-dimensional structure database, the molecular characterization of the TR/pMHC is made according to the IMGT Scientific chart rules that are based on the IMGT-ONTOLOGY concepts. IMGT/3Dstructure-DB provides the standardized IMGT gene and allele names (CLASSIFICATION), the standardized IMGT labels (DESCRIPTION), and the IMGT unique numbering (NUMEROTATION). As the IMGT structural unit is the domain, amino acids at conserved positions always have the same number in the IMGT® databases, tools, and Web resources. For the TR α and β chains, the amino acids in contact with the peptide/MHC (pMHC) are defined according to the IMGT unique numbering for V-DOMAIN. The MHC chain cleft that binds the peptide is formed by two groove domains (G-DOMAIN), each one comprising four antiparallel β strands and one α helix. The IMGT unique numbering for G-DOMAIN applies both to the first two domains (G-ALPHA1 and G-ALPHA2) of the MHC class I α chain, and to the first domain (G-ALPHA and G-BETA) of the MHC class II α chain and β chain, respectively. Based on the IMGT unique numbering, we defined 11 contact sites for the analysis of the pMHC contacts. The TR/pMHC contact description, based on the IMGT numbering, can be queried in the IMGT/StucturalQuery tool, at http://imgt.cines.fr.

Keywords

Major Histocompatibility Complex Major Histocompatibility Complex Class Major Histocompatibility Complex Molecule Complementarity Determine Region Major Histocompatibility Complex Allele 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Adams, H.P., and Koziol, J.A. (1995) Prediction of binding to MHC class I molecules. J. Immunol. Methods 185:181-190.PubMedCrossRefGoogle Scholar
  2. Apostolopoulos, V., Yu, M., Corper, A.L., Teyton, L., Pieters, G.A., McKenzie, I.F.C., and Wilson, I.A. (2002) Crystal structure of a non-canonical low-affinity peptide complexed with MHC class I: A new approach for vaccine design. J. Mol. Biol. 318:1293-1305.PubMedCrossRefGoogle Scholar
  3. Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N., and Bourne, P.E. (2000) The Protein Data Bank. Nucleic Acids Res. 28:235-242.PubMedCrossRefGoogle Scholar
  4. Blake, J.A., Richardson, J.E., Bult, C.J., Kadin, J.A., and Eppig, J.T. (2003) MGD: The Mouse Genome Database. Nucleic Acids Res. 31:193-195.PubMedCrossRefGoogle Scholar
  5. Blythe, M.J., Doytchinova, I.A., and Flower, D.R. (2002) JenPep: A database of quantitative functional peptide data for immunology. Bioinformatics 18:434-439.PubMedCrossRefGoogle Scholar
  6. Brusic, V., Rudy, G., and Harrison, L.C. (1998) MHCPEP, a database of MHC-binding peptides: Update 1997. Nucleic Acids Res. 26:368-371.PubMedCrossRefGoogle Scholar
  7. Buslepp, J., Wang, H., Biddison, W.E., Appella, E., and Collins, E.J. (2003) A correlation between TCR Vα docking on MHC and CD8 dependence: Implications for T cell selection. Immunity 19:595-606.PubMedCrossRefGoogle Scholar
  8. Davis, M.M. (2002) A new trigger for T cells. Cell 110:285-287.PubMedCrossRefGoogle Scholar
  9. Degano, M., Garcia, K.C., Apostolopoulos, V., Rudolph, M.G., Teyton, L., and Wilson, I.A. (2000) A functional hot spot for antigen recognition in a superagonist TCR/MHC complex. Immunity 12:251-261.PubMedCrossRefGoogle Scholar
  10. Ding, Y.H., Smith, K.J., Garboczi, D.N., Utz, U., Biddison, W.E., and Wiley, D.C. (1998) Two human T cell receptors bind in a similar diagonal mode to the HLA-A2/Tax peptide complex using different TCR amino acids. Immunity 8:403-411.PubMedCrossRefGoogle Scholar
  11. Ding, Y.H., Baker, B.M., Garboczi, D.N., Biddison, W.E., and Wiley, D.C. (1999) Four A6-TCR/peptide/HLA-A2 structures that generate very different T cell signals are nearly identical. Immunity 11:45-56.PubMedCrossRefGoogle Scholar
  12. Falk, K., Rotzschke, O., Stevanovic, S., Jung, G., and Rammensee, H.G. (1991) Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 351:290-296.PubMedCrossRefGoogle Scholar
  13. Garboczi, D.N., Ghosh, P., Utz, U., Fan, Q.R., Biddison, W.E., and Wiley, D.C. (1996) Structure of the complex between human T-cell receptor, viral peptide and HLA-A2. Nature 384:134-141.PubMedCrossRefGoogle Scholar
  14. Garcia, K.C., Degano, M., Pease, L.R., Huang, M., Peterson, P.A., Teyton, L., and Wilson, I.A. (1998) Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC. Antigen Sci. 279:1166-1172.Google Scholar
  15. Giudicelli, V., and Lefranc, M.-P. (1999) Ontology for immunogenetics: The IMGT-ONTOLOGY. Bioinformatics 15:1047-1054.PubMedCrossRefGoogle Scholar
  16. Giudicelli, V., Chaume, D., and Lefranc, M.-P. (2004) IMGT/V-QUEST, an integrated software program for immunoglobulin and T cell receptor V-J and V-D-J rearrangement analysis. Nucleic Acids Res. 32:435-440.CrossRefGoogle Scholar
  17. Giudicelli, V., Chaume, D., and Lefranc, M.-P. (2005) IMGT/GENE-DB: A comprehensive database for human and mouse immunoglobulin and T cell receptor genes. Nucleic Acids Res. 33:256-261.CrossRefGoogle Scholar
  18. Giudicelli, V., Ginestoux, C., Folch, G., Jabado-Michaloud, J., Chaume, D., and Lefranc, M.-P. (2006) IMGT/LIGM-DB, the IMGT® comprehensive database of immunoglobulin and T cell receptor nucleotide sequences. Nucleic Acids Res. 34:D781-D784.PubMedCrossRefGoogle Scholar
  19. Gulukota, K., Sidney, J., Sette, A., and DeLisi, C. (1997) Two complementary methods for predicting peptides binding major histocompatibility complex molecules. J. Mol. Biol. 267:1258-1267.PubMedCrossRefGoogle Scholar
  20. Hennecke, J., Carfi, A., and Wiley, D.C. (2000) Structure of a covalently stabilized complex of a human α β T-cell receptor, influenza HA peptide and MHC class II molecule, HLA-DR1. EMBO J. 19:5611-5624.PubMedCrossRefGoogle Scholar
  21. Hennecke, J., and Wiley, D.C. (2002) Structure of a complex of the human alpha/beta T cell receptor (TCR) HA1.7, influenza hemagglutinin peptide, and major histocompatibility complex class II molecule, HLA-DR4 (DRA*0101 and DRB1*0401): Insight into TCR cross-restriction and alloreactivity. J. Exp. Med. 195:571-581.PubMedCrossRefGoogle Scholar
  22. Irvine, D.J., Purbhoo, M.A., Krosgaard, M., and Davis, M.M. (2002) Direct observation of ligand recognition by T cells. Nature 419:845-849.PubMedCrossRefGoogle Scholar
  23. Kaas, Q., Ruiz, M., and Lefranc, M.-P. (2004) IMGT/3Dstructure-DB and IMGT/StructuralQuery, a database and a tool for immunoglobulin, T cell receptor and MHC structural data. Nucleic Acids Res. 32:208-210.CrossRefGoogle Scholar
  24. Kaas, Q., and Lefranc, M.-P. (2005) T cell receptor/peptide/MHC molecular characterization and standardized pMHC contact sites in IMGT/3Dstructure-DB. In Silico Biol. 5:505-528.PubMedGoogle Scholar
  25. Kjer-Nielsen, L., Clements, C.S., Purcell, A.W., Brooks, A.G., Whisstock, J.C., Burrows, S.R., McCluskey, J., and Rossjohn, J. (2003) A structural basis for the selection of dominant α β T cell receptors in antiviral immunity. Immunity 18:53-64.PubMedCrossRefGoogle Scholar
  26. Lawrence, M.C., and Colman, P.M. (1993) Shape complementarity at protein/protein interfaces. J. Mol. Biol. 234:946-950.PubMedCrossRefGoogle Scholar
  27. Lefranc, M.-P., and Lefranc, G. (2001) The T cell receptor FactsBook. Academic Press, London.Google Scholar
  28. Lefranc, M.-P. (2003a) IMGT, the international ImMunoGeneTics information system® (http://imgt.cines.fr). In: B.K.C. Lo (Ed.), Antibody Engineering: Methods and Protocols, 2nd edition. Methods in Molecular Biology. Humana Press, Totowa, NJ, 248, pp. 27-49.Google Scholar
  29. Lefranc, M.-P., Pommié, C., Ruiz, M., Giudicelli, V., Foulquier, E., Truong, L., Thouvenin-Contet, V., and Lefranc, G. (2003b) IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains. Dev. Comp. Immunol. 27:55-77.CrossRefGoogle Scholar
  30. Lefranc, M.-P. (2004a) IMGT-ONTOLOGY and IMGT databases, tools and Web resources for immunogenetics and immunoinformatics. Mol. Immunol. 40:647-660.CrossRefGoogle Scholar
  31. Lefranc, M.-P., Giudicelli, V., Ginestoux, C., Bosc, N., Folch, G., Guiraudou, D., Jabado-Michaloud, J., Magris, S., Scaviner, D., Thouvenin, V., Combres, K., Girod, D., Jeanjean, S., Protat, C., Monod, Y.M., Duprat, E., Kaas, Q., Pommié, C., Chaume, D., and Lefranc, G. (2004b) IMGT-ONTOLOGY for immunogenetics and immunoinformatics. In Silico Biol. 4:17-29.Google Scholar
  32. Lefranc, M.-P., Clément, O., Kaas, Q., Duprat, E., Chastellan, P., Coelho, I., Combres, K., Ginestoux, C., Giudicelli, V., Chaume, D., and Lefranc, G. (2005a) IMGT-Choreography for Immunogenetics and Immunoinformatics. In Silico Biol. 5:6.Google Scholar
  33. Lefranc, M.-P., Duprat, E., Kaas, Q., Tranne, M., Thiriot, A., and Lefranc, G. (2005b) IMGT unique numbering for MHC groove G-DOMAIN and MHC superfamily (MhcSF) G-LIKE-DOMAIN. Dev. Comp. Immunol. 29:917-938.CrossRefGoogle Scholar
  34. Lefranc, M.-P., Giudicelli, V., Kaas Q., Duprat, E., Jabado-Michaloud, J., Scaviner, D., Ginestoux, C., Clément, O., Chaume, D., and Lefranc, G. (2005c) IMGT, the international ImMunoGeneTics information system. Nucleic Acids Res. 33:D593-D597.CrossRefGoogle Scholar
  35. Lefranc, M.-P., Pommié, C., Kaas, Q., Duprat, E., Bosc, N., Guiraudou, D., Jean, C., Ruiz, M., Da Piedade, L., Rouard, M., Foulquier, E., Thouvenin, V., and Lefranc, G. (2005d) IMGT unique numbering for immunoglobulin and T cell receptor constant domains and Ig superfamily C-like domains. Dev. Comp. Immunol. 29:185-203.CrossRefGoogle Scholar
  36. Lesk, A.M., and Chothia, C. (1982) Evolution of proteins formed by β -sheets. II. The core of the immunoglobulin domains. J. Mol. Biol. 160:325-342.PubMedCrossRefGoogle Scholar
  37. Luz, J.G., Huang, M., Garcia, K.C., Rudolph, M.G., Apostolopoulos, V., Teyton, L., and Wilson, I.A. (2002) Structural comparison of allogeneic and syngeneic T cell receptor-peptide-major histocompatibility complex complexes: A buried alloreactive mutation subtly alters peptide presentation substantially increasing V(β) interactions. J. Exp. Med. 195:1175-1186.PubMedCrossRefGoogle Scholar
  38. Mandelboim, O., Bar-Haim, E., Vadai, E., Fridkin, M., and Eisenbach, L. (1997) Identification of shared tumor-associated antigen peptides between two spontaneous lung carcinomas. J. Immunol. 159:6030-6036.PubMedGoogle Scholar
  39. Rammensee, H.G., Bachmann, J., Emmerich, N.P.N., Bachor, O.A., and Stevanovie, S. (1999) SYFPEITHI: Database for MHC ligands and peptide motifs. Immunogenetics 50:213-219.PubMedCrossRefGoogle Scholar
  40. Reinherz, E.L., Tan, K., Tang, L., Kern, P., Liu, J., Xiong, Y., Hussey, R.E., Smolyar, A., Hare, B., Zhang, R., Joachimiak, A., Chang, H.C., Wagner, G., and Wang, J. (1999) The crystal structure of a T cell receptor in complex with peptide and MHC class II. Science 286:1913-1921.PubMedCrossRefGoogle Scholar
  41. Reiser, J.B., Darnault, C., Guimezanes, A., Gregoire, C., Mosser, T., Schmitt-Verhulst, A.M., Fontecilla-Camps, J.C., Malissen, B., Housset, D., and Mazza, G. (2000) Crystal structure of a T cell receptor bound to an allogeneic MHC molecule. Nat. Immunol. 1:291-297.PubMedCrossRefGoogle Scholar
  42. Reiser, J.B., Gregoire, C., Darnault, C., Mosser, T., Guimezanes, A., Schmitt-Verhulst, A.M., Fontecilla-Camps, J.C., Mazza, G., Malissen, B., and Housset, D. (2002) A T cell receptor CDR3β loop undergoes conformational changes of unprecedented magnitude upon binding to a peptide/MHC class I complex. Immunity 16:345-354.PubMedCrossRefGoogle Scholar
  43. Reiser, J.B., Darnault, C., Gregoire, C., Mosser, T., Mazza, G., Kearney, A., van der Merwe, P.A., Fontecilla-Camps, J.C., Housset, D., and Malissen, B. (2003) CDR3 loop flexibility contributes to the degeneracy of TCR recognition. Nat. Immunol. 4:241-247.PubMedCrossRefGoogle Scholar
  44. Robinson, J., Waller, M.J., Parham, P., de Groot, N., Bontrop, R., Kennedy, L.J., Stoehr, P., and Marsh, S.G. (2003) IMGT/HLA and IMGT/MHC: Sequence databases for the study of the major histocompatibility complex. Nucleic Acids Res. 31:311-314.PubMedCrossRefGoogle Scholar
  45. Rudolph, M.G., Luz, J.G., and Wilson, I.A. (2002) Structural and thermodynamic correlates of T cell signaling. Annu. Rev. Biophys. Biomol. Struct. 31:121-149.PubMedCrossRefGoogle Scholar
  46. Scott, C.A., Peterson, P.A., Teyton, L., and Wilson, I.A. (1998) Crystal structures of two I-Ad-peptide complexes reveal that high affinity can be achieved without large anchor residues. Immunity 8:319-329.PubMedCrossRefGoogle Scholar
  47. Sim, B.C., Zerva, L., Greene, M.I., and Gascoigne, N.R. (1996) Control of MHC restriction by TCR Vα CDR1 and CDR2. Science 273:963-964.PubMedCrossRefGoogle Scholar
  48. Singh, H., and Raghava, G.P. (2003) ProPred1: Prediction of promiscuous MHC class-I binding sites. Bioinformatics 19:1009-1014.Google Scholar
  49. Stewart-Jones, G.B.E., McMichael, A.J., Bell, J.I., Stuart, D.I., and Jones, E.Y. (2003) A structural basis for immunodominant human T cell receptor recognition. Nat. Immunol. 4:657-663.PubMedCrossRefGoogle Scholar
  50. Vasmatzis, G., Cornette, J., Sezerman, U., and DeLisi, C. (1996a) TcR recognition of the MHC-peptide dimer: Structural properties of a ternary complex. J. Mol. Biol. 261:72-89.Google Scholar
  51. Vasmatzis, G., Zhang, C., Cornette, J.L., and DeLisi, C. (1996b) Computational determination of side chain specificity for pockets in class I MHC molecules. Mol. Immunol. 33:1231-1239.CrossRefGoogle Scholar
  52. Wain, H.M., Bruford, E.A., Lovering, R.C., Lush, M.J., Wright, M.W., and Povey, S. (2002) Guidelines for human gene nomenclature. Genomics 79:464-470.PubMedCrossRefGoogle Scholar
  53. Wang, J.H., Meijers, R., Xiong, Y., Liu, J.H., Sakihama, T., Zhang, R., Joachimiak, A., and Reinherz, E.L. (2001) Crystal structure of the human CD4 N-terminal two-domain fragment complexed to a class II MHC molecule. Proc. Natl. Acad. Sci. USA 98:10799-10804.PubMedCrossRefGoogle Scholar
  54. Wang, J.H., and Reinherz, E.L. (2002) Structural basis of T cell recognition of peptides bound to MHC molecules. Mol. Immunol. 38:1039-1049.PubMedCrossRefGoogle Scholar
  55. Yousfi Monod, M., Giudicelli, V., Chaume, D., and Lefranc, M.-P. (2004) IMGT/JunctionAnalysis: The first tool for the analysis of the immunoglobulin and T cell receptor complex V-J and V-D-J junctions. Bioinformatics 20:I379-I385.PubMedCrossRefGoogle Scholar
  56. Zhang, C., Anderson, A., and DeLisi, C. (1998) Structural principles that govern the peptide-binding motifs of class I MHC molecules. J. Mol. Biol. 281:929-947.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Quentin Kaas
    • 1
  • Elodie Duprat
    • 1
  • Guillaume Tourneur
    • 1
  • Marie-Paule Lefranc
    • 1
    • 2
  1. 1.IMGT® the International ImMunoGeneTics Information System®Université Montpellier II, Laboratoire d’ImmunoGénétique Moléculaire LIGM, UPR CNRS 1142 Institut de Génétique Humaine IGH141 rue de la CardonilleFrance
  2. 2.Institut Universitaire de France103 Boulevard Saint-MichelFrance

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