A highly tilted binding mode by a self-reactive T cell receptor results in altered engagement of peptide and MHC

Journal of Experimental Medicine

Volumn 208, Issue 1, 2011, Pages 91-102

  Sethi, Dhruv K ^a   Schubert, David A ^a   Anders, Anne Kathrin ^a,b   Heroux, Annie ^c   Bonsor, Daniel A ^d   Thomas, Chantz P ^a   Sundberg, Eric J ^d   Pyrdol, Jason ^a   Wucherpfennig, Kai W ^a,b  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c BROOKHAVEN NATIONAL LABORATORY   (United States)

^d BOSTON BIOMEDICAL RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LIGAND; T LYMPHOCYTE RECEPTOR ALPHA CHAIN;

ARTICLE; COMPLEMENTARITY DETERMINING REGION; CROSS REACTION; CRYSTAL STRUCTURE; ESCAPE BEHAVIOR; GERMLINE MICRONUCLEUS; HUMAN; MAJOR HISTOCOMPATIBILITY COMPLEX; MOUSE; MULTIPLE SCLEROSIS; NONHUMAN; PRIORITY JOURNAL;

ANIMALS; HISTOCOMPATIBILITY ANTIGENS; HUMANS; MICE; MODELS, MOLECULAR; PEPTIDES; PROTEIN STRUCTURE, TERTIARY; RECEPTORS, ANTIGEN, T-CELL; STRUCTURAL HOMOLOGY, PROTEIN;

EID: 78651519759     PISSN: 00221007     EISSN: 15409538     Source Type: Journal    
DOI: 10.1084/jem.20100725     Document Type: Article

References (62)

1. Altschul, S.F., W. Gish, W. Miller, E.W. Myers, and D.J. Lipman. 1990. Basic local alignment search tool. J. Mol. Biol. 215:403-410.
2. Armstrong, K.M., K.H. Piepenbrink, and B.M. Baker. 2008. Conformational changes and flexibility in T-cell receptor recognition of peptide-MHC complexes. Biochem. J. 415:183-196. doi:10.1042/BJ20080850
3. Baker, B.M., and D.C. Wiley. 2001. alpha beta T cell receptor ligand-specific oligomerization revisited. Immunity. 14:681-692. doi:10.1016/S1074-7613(01)00160-1
4. Borg, N.A., L.K. Ely, T. Beddoe, W.A. Macdonald, H.H. Reid, C.S. Clements, A.W. Purcell, L. Kjer-Nielsen, J.J. Miles, S.R. Burrows, et al. 2005. The CDR3 regions of an immunodominant T cell receptor dictate the 'energetic landscape' of peptide-MHC recognition. Nat. Immunol. 6:171-180. doi:10.1038/ni1155
5. Boulter, J.M., M. Glick, P.T. Todorov, E. Baston, M. Sami, P. Rizkallah, and B.K. Jakobsen. 2003. Stable, soluble T-cell receptor molecules for crystallization and therapeutics. Protein Eng. 16:707-711. doi:10.1093/protein/ gzg087
6. Brunger, A.T. 2007. Version 1.2 of the Crystallography and NMR system. Nat. Protoc. 2:2728-2733. doi:10.1038/nprot.2007.406
7. Burrows, S.R., Z. Chen, J.K. Archbold, F.E. Tynan, T. Beddoe, L. Kjer-Nielsen, J.J. Miles, R. Khanna, D.J. Moss, Y.C. Liu, et al. 2010. Hard wiring of T cell receptor specificity for the major histocompatibility complex is underpinned by TCR adaptability. Proc. Natl. Acad. Sci. USA. 107:10608-10613. doi:10.1073/pnas.1004926107
8. Cole, D.K., N.J. Pumphrey, J.M. Boulter, M. Sami, J.I. Bell, E. Gostick, D.A. Price, G.F. Gao, A.K. Sewell, and B.K. Jakobsen. 2007. Human TCR-binding affinity is governed by MHC class restriction. J. Immunol. 178:5727-5734.
9. Collaborative Computational Project, Number 4. 1994. The CCP4 suite: programs for protein crystallography. Acta Crystallogr. D Biol. Crystallogr. 50:760-763. doi:10.1107/S0907444994003112
10. Costantini, S., A. Paladino, and A.M. Facchiano. 2008. CALCOM: a software for calculating the center of mass of proteins. Bioinformation. 2:271-272.
11. Dai, S., E.S. Huseby, K. Rubtsova, J. Scott-Browne, F. Crawford, W.A. Macdonald, P. Marrack, and J.W. Kappler. 2008. Crossreactive T Cells spotlight the germline rules for alphabeta T cell-receptor interactions with MHC molecules. Immunity. 28:324-334. doi:10.1016/j.immuni.2008.01.008
12. Day, C.L., N.P. Seth, M. Lucas, H. Appel, L. Gauthier, G.M. Lauer, G.K. Robbins, Z.M. Szczepiorkowski, D.R. Casson, R.T. Chung, et al. 2003. Ex vivo analysis of human memory CD4 T cells specific for hepatitis C virus using MHC class II tetramers. J. Clin. Invest. 112:831-842.
13. Ellmerich, S., M. Mycko, K. Takacs, H. Waldner, F.N. Wahid, R.J. Boyton, R.H. King, P.A. Smith, S. Amor, A.H. Herlihy, et al. 2005. High incidence of spontaneous disease in an HLA-DR15 and TCR transgenic multiple sclerosis model. J. Immunol. 174:1938-1946.
14. Emsley, P., and K. Cowtan. 2004. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60:2126-2132. doi:10.1107/S0907444904019158
15. Fairchild, P.J., R. Wildgoose, E. Atherton, S. Webb, and D.C. Wraith. 1993. An autoantigenic T cell epitope forms unstable complexes with class II MHC: a novel route for escape from tolerance induction. Int. Immunol. 5:1151-1158. doi:10.1093/intimm/5.9.1151
16. Feng, D., C.J. Bond, L.K. Ely, J. Maynard, and K.C. Garcia. 2007. Structural evidence for a germline-encoded T cell receptor-major histocompatibility complex interaction 'codon'. Nat. Immunol. 8:975-983. doi:10.1038/ni1502
17. Garboczi, D.N., P. Ghosh, U. Utz, Q.R. Fan, W.E. Biddison, and D.C. Wiley. 1996. Structure of the complex between human T-cell receptor, viral peptide and HLA-A2. Nature. 384:134-141. doi:10.1038/384134a0
18. Garcia, K.C., and E.J. Adams. 2005. How the T cell receptor sees antigen - a structural view. Cell. 122:333-336. doi:10.1016/j.cell.2005.07.015
19. Garcia, K.C., M. Degano, R.L. Stanfield, A. Brunmark, M.R. Jackson, P.A. Peterson, L. Teyton, and I.A. Wilson. 1996. An alphabeta T cell receptor structure at 2.5 A and its orientation in the TCR-MHC complex. Science. 274:209-219. doi:10.1126/science.274.5285.209
20. Garcia, K.C., M. Degano, L.R. Pease, M. Huang, P.A. Peterson, L. Teyton, and I.A. Wilson. 1998. Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC antigen. Science. 279:1166-1172. doi:10.1126/science.279.5354.1166
21. Garcia, K.C., J.J. Adams, D. Feng, and L.K. Ely. 2009. The molecular basis of TCR germline bias for MHC is surprisingly simple. Nat. Immunol. 10:143-147. doi:10.1038/ni.f.219
22. Goverman, J., A. Woods, L. Larson, L.P. Weiner, L. Hood, and D.M. Zaller. 1993. Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity. Cell. 72:551-560. doi:10.1016/0092-8674(93)90074-Z
23. Gras, S., S.R. Burrows, L. Kjer-Nielsen, C.S. Clements, Y.C. Liu, L.C. Sullivan, M.J. Bell, A.G. Brooks, A.W. Purcell, J. McCluskey, and J. Rossjohn. 2009. The shaping of T cell receptor recognition by self-tolerance. Immunity. 30:193-203. doi:10.1016/j.immuni.2008.11.011
24. Hahn, M., M.J. Nicholson, J. Pyrdol, and K.W. Wucherpfennig. 2005. Unconventional topology of self peptide-major histocompatibility complex binding by a human autoimmune T cell receptor. Nat. Immunol. 6:490-496. doi:10.1038/ni1187
25. Hare, B.J., D.F. Wyss, M.S. Osburne, P.S. Kern, E.L. Reinherz, and G. Wagner. 1999. Structure, specificity and CDR mobility of a class II restricted single-chain T-cell receptor. Nat. Struct. Biol. 6:574-581. doi:10.1038/9359
26. Harrington, C.J., A. Paez, T. Hunkapiller, V. Mannikko, T. Brabb, M. Ahearn, C. Beeson, and J. Goverman. 1998. Differential tolerance is induced in T cells recognizing distinct epitopes of myelin basic protein. Immunity. 8:571-580. doi:10.1016/S1074-7613(00)80562-2
27. He, X.L., C. Radu, J. Sidney, A. Sette, E.S. Ward, and K.C. Garcia. 2002. Structural snapshot of aberrant antigen presentation linked to autoimmunity: the immunodominant epitope of MBP complexed with I-Au. Immunity. 17:83-94. doi:10.1016/S1074-7613(02)00340-0
28. Hennecke, J., A. Carfi, and D.C. Wiley. 2000. Structure of a covalently stabilized complex of a human alphabeta T-cell receptor, influenza HA peptide and MHC class II molecule, HLA-DR1. EMBO J. 19:5611-5624. doi:10.1093/emboj/19. 21.5611
29. Huseby, E.S., J. White, F. Crawford, T. Vass, D. Becker, C. Pinilla, P. Marrack, and J.W. Kappler. 2005. How the T cell repertoire becomes peptide and MHC specific. Cell. 122:247-260. doi:10.1038/ni1401
30. Huseby, E.S., F. Crawford, J. White, P. Marrack, and J.W. Kappler. 2006. Interface-disrupting amino acids establish specificity between T cell receptors and complexes of major histocompatibility complex and peptide. Nat. Immunol. 7:1191-1199. doi:10.1038/ni1401
31. Ishikura, H., N. Ishikawa, and M. Aizawa. 1987. Differential expression of HLA-class II antigens in the human thymus. Relative paucity of HLA-DQ antigens in the thymic medulla. Transplantation. 44:314-317. doi:10.1097/00007890-198708000-00026
32. Lafaille, J.J., K. Nagashima, M. Katsuki, and S. Tonegawa. 1994. High incidence of spontaneous autoimmune encephalomyelitis in immunodeficient anti-myelin basic protein T cell receptor transgenic mice. Cell. 78:399-408. doi:10.1016/0092-8674(94)90419-7
33. Laskowski, R.A., M.W. MacArthur, D.S. Moss, and J.M. Thornton. 1993. PROCHECK - a program to check the stereochemical quality of protein structures. J. Appl. Crystallogr. 26:283-291. doi:10.1107/S0021889892009944
34. Lee, B., and F.M. Richards. 1971. The interpretation of protein structures: estimation of static accessibility. J. Mol. Biol. 55:379-400. doi:10.1016/0022-2836(71)90324-X
35. Li, Y., Y. Huang, J. Lue, J.A. Quandt, R. Martin, and R.A. Mariuzza. 2005. Structure of a human autoimmune TCR bound to a myelin basic protein self-peptide and a multiple sclerosis-associated MHC class II molecule. EMBO J. 24:2968-2979. doi:10.1038/sj.emboj.7600771
36. Madsen, L.S., E.C. Andersson, L. Jansson, M. krogsgaard, C.B. Andersen, J. Engberg, J.L. Strominger, A. Svejgaard, J.P. Hjorth, R. Holmdahl, et al. 1999. A humanized model for multiple sclerosis using HLA-DR2 and a human T-cell receptor. Nat. Genet. 23:343-347. doi:10.1038/15525
37. Manning, T.C., C.J. Schlueter, T.C. Brodnicki, E.A. Parke, J.A. Speir, K.C. Garcia, L. Teyton, I.A. Wilson, and D.M. Kranz. 1998. Alanine scanning mutagenesis of an alphabeta T cell receptor: mapping the energy of antigen recognition. Immunity. 8:413-425. doi:10.1016/S1074-7613(00)80547-6
38. Marrack, P., J.P. Scott-Browne, S. Dai, L. Gapin, and J.W. Kappler. 2008. Evolutionarily conserved amino acids that control TCR-MHC interaction. Annu. Rev. Immunol. 26:171-203. doi:10.1146/annurev.immunol.26.021607.090421
39. Maynard, J., K. Petersson, D.H. Wilson, E.J. Adams, S.E. Blondelle, M.J. Boulanger, D.B. Wilson, and K.C. Garcia. 2005. Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: insights into MHC bias and antigen specificity. Immunity. 22:81-92.
40. McCoy, A.J., R.W. Grosse-Kunstleve, P.D. Adams, M.D. Winn, L.C. Storoni, and R.J. Read. 2007. Phaser crystallographic software. J. Appl. Cryst. 40:658-674. doi:10.1107/S0021889807021206
41. Otwinowski, Z., and W. Minor. 1997. Processing of x-ray diffraction data collected in oscillation mode. Methods Enzymol. 276:307-326. doi:10.1016/S0076-6879(97)76066-X
42. Pearson, C.I., W. van Ewijk, and H.O. McDevitt. 1997. Induction of apoptosis and T helper 2 (Th2) responses correlates with peptide affinity for the major histocompatibility complex in self-reactive T cell receptor transgenic mice. J. Exp. Med. 185:583-599. doi:10.1084/jem.185.4.583
43. Reinherz, E.L., K. Tan, L. Tang, P. Kern, J. Liu, Y. Xiong, R.E. Hussey, A. Smolyar, B. Hare, R. Zhang, et al. 1999. The crystal structure of a T cell receptor in complex with peptide and MHC class II. Science. 286:1913-1921. doi:10.1126/science.286.5446.1913
44. Reiser, J.B., C. Darnault, A. Guimezanes, C. Grégoire, T. Mosser, A.M. Schmitt-Verhulst, J.C. Fontecilla-Camps, B. Malissen, D. Housset, and G. Mazza. 2000. Crystal structure of a T cell receptor bound to an allogeneic MHC molecule. Nat. Immunol. 1:291-297. doi:10.1038/79728
45. Roucard, C., F. Garban, N.A. Mooney, D.J. Charron, and M.L. Ericson. 1996. Conformation of human leukocyte antigen class II molecules. Evidence for superdimers and empty molecules on human antigen presenting cells. J. Biol. Chem. 271:13993-14000. doi:10.1074/jbc.271.24.13993
46. Rudolph, M.G., R.L. Stanfield, and I.A. Wilson. 2006. How TCRs bind MHCs, peptides, and coreceptors. Annu. Rev. Immunol. 24:419-466. doi:10.1146/annurev. immunol.23.021704.115658
47. Scott-Browne, J.P., J. White, J.W. Kappler, L. Gapin, and P. Marrack. 2009. Germline-encoded amino acids in the alphabeta T-cell receptor control thymic selection. Nature. 458:1043-1046. doi:10.1038/nature07812
48. Siebold, C., B.E. Hansen, J.R. Wyer, K. Harlos, R.E. Esnouf, A. Svejgaard, J.I. Bell, J.L. Strominger, E.Y. Jones, and L. Fugger. 2004. Crystal structure of HLA-DQ0602 that protects against type 1 diabetes and confers strong susceptibility to narcolepsy. Proc. Natl. Acad. Sci. USA. 101:1999-2004. doi:10.1073/pnas.0308458100
49. Sim, B.C., L. Zerva, M.I. Greene, and N.R. Gascoigne. 1996. Control of MHC restriction by TCR Valpha CDR1 and CDR2. Science. 273:963-966. doi:10.1126/science.273.5277.963
50. Smith, K.J., J. Pyrdol, L. Gauthier, D.C. Wiley, and K.W. Wucherpfennig. 1998. Crystal structure of HLA-DR2 (DRA*0101, DRB1*1501) complexed with a peptide from human myelin basic protein. J. Exp. Med. 188:1511-1520. doi:10.1084/jem.188.8.1511
51. Stanley, P. 1989. Chinese hamster ovary cell mutants with multiple glycosylation defects for production of glycoproteins with minimal carbohydrate heterogeneity. Mol. Cell. Biol. 9:377-383.
52. Sun, R., S.E. Shepherd, S.S. Geier, C.T. Thomson, J.M. Sheil, and S.G. Nathenson. 1995. Evidence that the antigen receptors of cytotoxic T lymphocytes interact with a common recognition pattern on the H-2Kb molecule. Immunity. 3:573-582. doi:10.1016/1074-7613(95)90128-0
53. Teng, M.K., A. Smolyar, A.G. Tse, J.H. Liu, J. Liu, R.E. Hussey, S.G. Nathenson, H.C. Chang, E.L. Reinherz, and J.H. Wang. 1998. Identification of a common docking topology with substantial variation among different TCR-peptide-MHC complexes. Curr. Biol. 8:409-412. doi:10.1016/S0960-9822(98) 70160-5
54. Turner, S.J., P.C. Doherty, J. McCluskey, and J. Rossjohn. 2006. Structural determinants of T-cell receptor bias in immunity. Nat. Rev. Immunol. 6:883-894. doi:10.1038/nri1977
55. Tynan, F.E., S.R. Burrows, A.M. Buckle, C.S. Clements, N.A. Borg, J.J. Miles, T. Beddoe, J.C. Whisstock, M.C. Wilce, S.L. Silins, et al. 2005. T cell receptor recognition of a 'super-bulged' major histocompatibility complex class I-bound peptide. Nat. Immunol. 6:1114-1122. doi:10.1038/ni1257
56. Tynan, F.E., H.H. Reid, L. Kjer-Nielsen, J.J. Miles, M.C. Wilce, L. Kostenko, N.A. Borg, N.A. Williamson, T. Beddoe, A.W. Purcell, et al. 2007. A T cell receptor flattens a bulged antigenic peptide presented by a major histocompatibility complex class I molecule. Nat. Immunol. 8:268-276. doi:10.1038/ni1432
57. Vagin, A., and A. Teplyakov. 1997. MOLREP: an automated program for molecular replacement. J. Appl. Crystallogr. 30:1022-1025. doi:10.1107/ S0021889897006766
58. Wu, L.C., D.S. Tuot, D.S. Lyons, K.C. Garcia, and M.M. Davis. 2002. Two-step binding mechanism for T-cell receptor recognition of peptide MHC. Nature. 418:552-556. doi:10.1038/nature00920
59. Wucherpfennig, K.W., and J.L. Strominger. 1995. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell. 80:695-705. doi:10.1016/0092-8674(95)90348-8
60. Wucherpfennig, K.W., A. Sette, S. Southwood, C. Oseroff, M. Matsui, J.L. Strominger, and D.A. Hafler. 1994a. Structural requirements for binding of an immunodominant myelin basic protein peptide to DR2 isotypes and for its recognition by human T cell clones. J. Exp. Med. 179:279-290. doi:10.1084/jem.179.1.279
61. Wucherpfennig, K.W., J. Zhang, C. Witek, M. Matsui, Y. Modabber, K. Ota, and D.A. Hafler. 1994b. Clonal expansion and persistence of human T cells specific for an immunodominant myelin basic protein peptide. J. Immunol. 152:5581-5592.
62. Wucherpfennig, K.W., M.J. Call, L. Deng, and R. Mariuzza. 2009. Structural alterations in peptide-MHC recognition by self-reactive T cell receptors. Curr. Opin. Immunol. 21:590-595. doi:10.1016/j.coi.2009.07.008