t Is a Structurally Novel Crohn's Disease-Associated Superantigen

English version České info

T cell responses to enteric bacteria are important in inflammatory bowel disease. I2, encoded by the pfiT gene of Pseudomonas fluorescens, is a T-cell superantigen associated with human Crohn's disease. Here we report the crystal structure of pfiT at 1.7Å resolution and provide a functional analysis of the interaction of pfiT and its homolog, PA2885, with human class II MHC. Both pfiT and PA2885 bound to mammalian cells and stimulated the proliferation of human lymphocytes. This binding was greatly inhibited by anti-class II MHC HLA-DR antibodies, and to a lesser extent, by anti HLA-DQ and DP antibodies, indicating that the binding was class II MHC-specific. GST-pfiT efficiently precipitated both endogenous and in vitro purified recombinant HLA-DR1 molecules, indicating that pfiT directly interacted with HLA-DR1. Competition studies revealed that pfiT and the superantigen Mycoplasma arthritidis mitogen (MAM) competed for binding to HLA-DR, indicating that their binding sites overlap. Structural analyses established that pfiT belongs to the TetR-family of DNA-binding transcription regulators. The distinct structure of pfiT indicates that it represents a new family of T cell superantigens.

Vyšlo v časopise: t Is a Structurally Novel Crohn's Disease-Associated Superantigen. PLoS Pathog 9(12): e32767. doi:10.1371/journal.ppat.1003837
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003837

Souhrn

Zdroje

1. KapplerJW, PullenA, CallahanJ, ChoiY, HermanA, et al. (1989) Consequences of self and foreign superantigen interaction with specific V beta elements of the murine TCR alpha beta. Cold Spring Harb Symp Quant Biol 54 Pt 1: 401–407.

2. MarrackP, KapplerJ (1990) The staphylococcal enterotoxins and their relatives. Science 248: 1066.

3. KotzinBL, LeungDY, KapplerJ, MarrackP (1993) Superantigens and their potential role in human disease. Adv Immunol 54: 99–166.

4. LiH, LleraA, MalchiodiEL, MariuzzaRA (1999) The structural basis of T cell activation by superantigens. Annu Rev Immunol 17: 435–466.

5. McCormickJK, YarwoodJM, SchlievertPM (2001) Toxic shock syndrome and bacterial superantigens: an update. Annu Rev Microbiol 55: 77–104.

6. PeterssonK, PetterssonH, SkartvedNJ, WalseB, ForsbergG (2003) Staphylococcal enterotoxin h induces valpha-specific expansion of T cells. J Immunol 170: 4148–4154.

7. WangLM, ZhaoYW, LiZ, GuoY, LindsayJL, et al. (2007) Crystal Structure of a Complete Ternary Complex Between T-Cell Receptor, Superantigen, and peptide-MHC Class II Molecule. Nat Struct & Mol Biol 14: 169–171.

8. SalineM, RodstromKE, FischerG, OrekhovVY, KarlssonBG, et al. (2010) The structure of superantigen complexed with TCR and MHC reveals novel insights into superantigenic T cell activation. Nature communications 1: 119.

9. DalwadiH, WeiB, KronenbergM, SuttonCL, BraunJ (2001) The Crohn's disease-associated bacterial protein I2 is a novel enteric t cell superantigen. Immunity 15: 149–158.

10. SuttonCL, KimJ, YamaneA, DalwadiH, WeiB, et al. (2000) Identification of a novel bacterial sequence associated with Crohn's disease. Gastroenterology 119: 23–31.

11. WeiB, HuangT, DalwadiH, SuttonCL, BrucknerD, et al. (2002) Pseudomonas fluorescens encodes the Crohn's disease-associated I2 sequence and T-cell superantigen. Infect Immun 70: 6567–6575.

12. LandersCJ, CohavyO, MisraR, YangH, LinYC, et al. (2002) Selected loss of tolerance evidenced by Crohn's disease-associated immune responses to auto- and microbial antigens. Gastroenterology 123: 689–699.

13. ArnottID, LandersCJ, NimmoEJ, DrummondHE, SmithBK, et al. (2004) Sero-reactivity to microbial components in Crohn's disease is associated with disease severity and progression, but not NOD2/CARD15 genotype. Am J Gastroenterol 99: 2376–2384.

14. IltanenS, TervoL, HalttunenT, WeiB, BraunJ, et al. (2006) Elevated serum anti-I2 and anti-OmpW antibody levels in children with IBD. Inflamm Bowel Dis 12: 389–394.

15. SpivakJ, LandersCJ, VasiliauskasEA, AbreuMT, DubinskyMC, et al. (2006) Antibodies to I2 predict clinical response to fecal diversion in Crohn's disease. Inflamm Bowel Dis 12: 1122–1130.

16. MundwilerML, MeiL, LandersCJ, ReveilleJD, TarganS, et al. (2009) Inflammatory bowel disease serologies in ankylosing spondylitis patients: a pilot study. Arthritis research & therapy 11: R177.

17. AshornS, ValinevaT, KaukinenK, AshornM, BraunJ, et al. (2009) Serological responses to microbial antigens in celiac disease patients during a gluten-free diet. Journal of clinical immunology 29: 190–195.

18. SuzukiH, FukudaY, KoizukaH, TomitaT, HoriK, et al. (2008) Dietary antigens in Crohn's disease: antibodies to porcine pancreatic amylase. The American journal of gastroenterology 103: 656–664.

19. MowWS, VasiliauskasEA, LinYC, FleshnerPR, PapadakisKA, et al. (2004) Association of antibody responses to microbial antigens and complications of small bowel Crohn's disease. Gastroenterology 126: 414–424.

20. MorganXC, TickleTL, SokolH, GeversD, DevaneyKL, et al. (2012) Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome biology 13: R79.

21. KimSC, TonkonogySL, AlbrightCA, TsangJ, BalishEJ, et al. (2005) Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria. Gastroenterology 128: 891–906.

22. Etongue-MayerP, LangloisMA, OuelletteM, LiH, YounesS, et al. (2002) Involvement of zinc in the binding of mycoplasma arthritidis-derived mitogen to the proximity of the HLA-DR binding groove regardless of histidine 81 of the beta chain. Eur J Immunol 32: 50–58.

23. BaccalaR, SmithLR, VestbergM, PetersonPA, ColeBC, et al. (1992) Mycoplasma arthritidis mitogen. V beta engaged in mice, rats, and humans, and requirement of HLA-DR alpha for presentation. Arthritis Rheum 35: 434–442.

24. ZhaoY, LiZ, DrozdS, GuoY, MouradW, et al. (2004) Crystal structure of Mycoplasma arthritidis mitogen complexed with HLA-DR1 reveals a novel superantigen fold and a dimerized superantigen-MHC complex. Structure 12: 277–288.

25. LiHM, ZhaoY, GuoY, LiZ, EiseleL, et al. (2007) Zinc induces dimerization of the class II MHC molecule that leads to cooperative binding to a superantigen. J Biol Chem 282: 5991–6000.

26. SchuckP, PeruginiMA, GonzalesNR, HowlettGJ, SchubertD (2002) Size-distribution analysis of proteins by analytical ultracentrifugation: strategies and application to model systems. Biophys J 82: 1096–1111.

27. VisticaJ, DamJ, BalboA, YikilmazE, MariuzzaRA, et al. (2004) Sedimentation equilibrium analysis of protein interactions with global implicit mass conservation constraints and systematic noise decomposition. Anal Biochem 326: 234–256.

28. GibratJF, MadejT, BryantSH (1996) Surprising similarities in structure comparison. Curr Opin Struct Biol 6: 377–385.

29. RamosJL, Martinez-BuenoM, Molina-HenaresAJ, TeranW, WatanabeK, et al. (2005) The TetR family of transcriptional repressors. Microbiology and molecular biology reviews : MMBR 69: 326–356.

30. Martinez-BuenoM, Molina-HenaresAJ, ParejaE, RamosJL, TobesR (2004) BacTregulators: a database of transcriptional regulators in bacteria and archaea. Bioinformatics 20: 2787–2791.

31. HinrichsW, KiskerC, DuvelM, MullerA, TovarK, et al. (1994) Structure of the Tet repressor-tetracycline complex and regulation of antibiotic resistance. Science 264: 418–420.

32. OrthP, SchnappingerD, HillenW, SaengerW, HinrichsW (2000) Structural basis of gene regulation by the tetracycline inducible Tet repressor-operator system. Nat Struct Biol 7: 215–219.

33. MillerDJ, ZhangYM, SubramanianC, RockCO, WhiteSW (2010) Structural basis for the transcriptional regulation of membrane lipid homeostasis. Nature structural & molecular biology 17: 971–975.

34. SchumacherMA, MillerMC, GrkovicS, BrownMH, SkurrayRA, et al. (2001) Structural mechanisms of QacR induction and multidrug recognition. Science 294: 2158–2163.

35. GuR, SuCC, ShiF, LiM, McDermottG, et al. (2007) Crystal structure of the transcriptional regulator CmeR from Campylobacter jejuni. Journal of Molecular Biology 372: 583–593.

36. AlguelY, LuD, QuadeN, SauterS, ZhangX (2010) Crystal structure of MexZ, a key repressor responsible for antibiotic resistance in Pseudomonas aeruginosa. Journal of structural biology 172: 305–310.

37. SchumacherMA, MillerMC, GrkovicS, BrownMH, SkurrayRA, et al. (2002) Structural basis for cooperative DNA binding by two dimers of the multidrug-binding protein QacR. Embo J 21: 1210–1218.

38. EuzebyJP (1997) List of Bacterial Names with Standing in Nomenclature: a folder available on the Internet. International journal of systematic bacteriology 47: 590–592.

39. LoperJE, HassanKA, MavrodiDV, DavisEW2nd, LimCK, et al. (2012) Comparative genomics of plant-associated Pseudomonas spp.: insights into diversity and inheritance of traits involved in multitrophic interactions. PLoS genetics 8: e1002784.

40. SilbyMW, Cerdeno-TarragaAM, VernikosGS, GiddensSR, JacksonRW, et al. (2009) Genomic and genetic analyses of diversity and plant interactions of Pseudomonas fluorescens. Genome biology 10: R51.

41. KimbrelJA, GivanSA, HalgrenAB, CreasonAL, MillsDI, et al. (2010) An improved, high-quality draft genome sequence of the Germination-Arrest Factor-producing Pseudomonas fluorescens WH6. BMC genomics 11: 522.

42. OrtetP, BarakatM, LalaounaD, FochesatoS, BarbeV, et al. (2011) Complete genome sequence of a beneficial plant root-associated bacterium, Pseudomonas brassicacearum. Journal of bacteriology 193: 3146.

43. PaulsenIT, PressCM, RavelJ, KobayashiDY, MyersGS, et al. (2005) Complete genome sequence of the plant commensal Pseudomonas fluorescens Pf-5. Nature biotechnology 23: 873–878.

44. MorgulisA, CoulourisG, RaytselisY, MaddenTL, AgarwalaR, et al. (2008) Database indexing for production MegaBLAST searches. Bioinformatics 24: 1757–1764.

45. ColeBC, SawitzkeAD, AhmedEA, AtkinCL, DavidCS (1997) Allelic polymorphisms at the H-2A and HLA-DQ loci influence the response of murine lymphocytes to the Mycoplasma arthritidis superantigen MAM. Infect Immun 65: 4190–4198.

46. DonadiniR, LiewCW, KwanAH, MackayJP, FieldsBA (2004) Crystal and solution structures of a superantigen from Yersinia pseudotuberculosis reveal a jelly-roll fold. Structure 12: 145–156.

47. MendozaJL, AbreuMT (2009) Biological markers in inflammatory bowel disease: practical consideration for clinicians. Gastroenterol Clin Biol 33 Suppl 3: S158–173.

48. PrideauxL, De CruzP, NgSC, KammMA (2012) Serological antibodies in inflammatory bowel disease: a systematic review. Inflamm Bowel Dis 18: 1340–1355.

49. HouJK, AbrahamB, El-SeragH (2011) Dietary intake and risk of developing inflammatory bowel disease: a systematic review of the literature. Am J Gastroenterol 106: 563–573.

50. SmithPM, HowittMR, PanikovN, MichaudM, GalliniCA, et al. (2013) The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341: 569–573.

51. RayD, ShahA, TilgnerM, GuoY, ZhaoY, et al. (2006) West Nile virus 5′-cap structure is formed by sequential guanine N-7 and ribose 2′-O methylations by nonstructural protein 5. Journal of virology 80: 8362–8370.

52. OtwinowskiZ, MinorW (1997) Processing of X-ray diffraction data collected in oscillation mode. Methods in Enzymology 276: 307–326.

53. TerwilligerTC, BerendzenJ (1999) Automated structure solution for MIR and MAD. Acta Crystallogr D Biol Crystallogr D55: 849–861.

54. TerwilligerTC (2000) Maximum-likelihood density modification. Acta Crystallogr D Biol Crystallogr 56(Pt 8): 965–972.

55. Roussel A, Cambillau C (1989) TURBO FRODO. Silicon Graphics Geometry Partners Directory. Mountain View, CA: Silicon Graphics. pp. 77–78.

56. AdamsPD, AfoninePV, BunkocziG, ChenVB, DavisIW, et al. (2010) PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66: 213–221.

57. NichollsA, SharpKA, HonigB (1991) Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons. Proteins 11: 281–296.