Identifying diagnostic peptides for lyme disease through epitope discovery.

G A Kouzmitcheva, V A Petrenko, G P Smith
Author Information
  1. G A Kouzmitcheva: Division of Biological Sciences, Tucker Hall, University of Missouri, Columbia, Missouri 65211, USA.

Abstract

Serum antibodies from patients with Lyme disease (LD) were used to affinity select peptide epitopes from 12 large random peptide libraries in phage display format. The selected peptides were surveyed for reactivity with a panel of positive sera (from LD patients) and negative sera (from subjects without LD), thus identifying 17 peptides with a diagnostically useful binding pattern: reactivity with at least three positive sera and no reactivity with any of the negative sera. The peptides define eight sequence motifs, none of which can be matched convincingly with segments of proteins from Borrelia burgdorferi, the LD pathogen; evidently, then, they are "mimotopes," mimicking natural pathogen epitopes without matching contiguous amino acids of pathogen proteins. Peptides like these could be the basis of a new diagnostic enzyme-linked immunosorbent assay for LD, with sufficient specificity and sensitivity to replace expensive immunoblotting tests that are currently required for definitive serological diagnosis. Moreover, the method used to discover these peptides did not require any knowledge of the pathogen and involved generic procedures that are applicable to almost any infectious disease, including emerging diseases for which no pathogen has yet been identified.

References

  1. J Med Microbiol. 1994 Apr;40(4):293-302 [PMID: 8151682]
  2. J Clin Microbiol. 1995 Oct;33(10):2596-600 [PMID: 8567889]
  3. J Immunol. 1996 Jun 1;156(11):4504-13 [PMID: 8666827]
  4. J Infect Dis. 1996 Aug;174(2):346-53 [PMID: 8699065]
  5. Methods Enzymol. 1996;267:3-27 [PMID: 8743307]
  6. J Clin Microbiol. 1996 Feb;34(2):237-40 [PMID: 8788993]
  7. Med Microbiol Immunol. 1996 May;185(1):49-57 [PMID: 8803953]
  8. Bioconjug Chem. 1996 May-Jun;7(3):338-42 [PMID: 8816957]
  9. J Autoimmun. 1996 Jun;9(3):431-6 [PMID: 8816983]
  10. Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11063-7 [PMID: 8855309]
  11. J Clin Microbiol. 1996 Oct;34(10):2343-50 [PMID: 8880477]
  12. Protein Eng. 1996 Sep;9(9):797-801 [PMID: 8888146]
  13. Emerg Infect Dis. 1996 Apr-Jun;2(2):136-40 [PMID: 8903216]
  14. J Immunol Methods. 1996 Oct 30;198(1):25-33 [PMID: 8914594]
  15. FEBS Lett. 1996 Dec 16;399(3):237-40 [PMID: 8985153]
  16. Infection. 1996 Nov-Dec;24(6):470-2 [PMID: 9007597]
  17. Gene. 1980 Apr;9(1-2):127-40 [PMID: 6247241]
  18. Gene. 1984 Dec;32(3):369-79 [PMID: 6099322]
  19. Ciba Found Symp. 1986;119:130-49 [PMID: 2426049]
  20. Mol Immunol. 1986 Jul;23(7):709-15 [PMID: 2432410]
  21. N Engl J Med. 1989 Aug 31;321(9):586-96 [PMID: 2668764]
  22. Science. 1990 Jul 27;249(4967):386-90 [PMID: 1696028]
  23. MMWR Recomm Rep. 1990 Oct 19;39(RR-13):1-43 [PMID: 2122225]
  24. Pediatrics. 1991 Sep;88(3):465-70 [PMID: 1881724]
  25. Arch Intern Med. 1991 Sep;151(9):1837-40 [PMID: 1888250]
  26. Blood. 1992 Feb 1;79(3):826-31 [PMID: 1310064]
  27. J Clin Microbiol. 1992 Feb;30(2):370-6 [PMID: 1537905]
  28. J Infect Dis. 1992 Jun;165(6):1127-32 [PMID: 1583333]
  29. JAMA. 1992 Aug 19;268(7):891-5 [PMID: 1640618]
  30. J Clin Epidemiol. 1992 Nov;45(11):1229-36 [PMID: 1432003]
  31. J Clin Microbiol. 1992 Dec;30(12):3158-62 [PMID: 1280650]
  32. J Infect Dis. 1993 Feb;167(2):392-400 [PMID: 8380611]
  33. Methods Enzymol. 1993;217:228-57 [PMID: 7682645]
  34. Eur J Immunol. 1993 Dec;23(12):3189-93 [PMID: 7504991]
  35. J Immunol Methods. 1994 May 2;171(1):103-9 [PMID: 7513731]
  36. EMBO J. 1994 May 1;13(9):2236-43 [PMID: 7514533]
  37. J Clin Microbiol. 1994 May;32(5):1154-8 [PMID: 8051239]
  38. Trends Biotechnol. 1994 Jul;12(7):262-7 [PMID: 7519861]
  39. Eur J Clin Microbiol Infect Dis. 1994 May;13(5):394-400 [PMID: 8070452]
  40. Gene. 1994 Sep 2;146(2):191-8 [PMID: 8076818]
  41. Clin Exp Immunol. 1994 Dec;98(3):520-5 [PMID: 7994916]
  42. J Infect Dis. 1995 Mar;171(3):724-7 [PMID: 7876628]
  43. Clin Immunol Immunopathol. 1995 Apr;75(1):45-50 [PMID: 7533685]
  44. J Immunol. 1995 Apr 1;154(7):3162-72 [PMID: 7534789]
  45. Am J Med. 1995 Apr 24;98(4A):10S-12S; discussion 12S-14S [PMID: 7726186]
  46. J Rheumatol. 1995 Apr;22(4):684-8 [PMID: 7791164]
  47. MMWR Morb Mortal Wkly Rep. 1995 Aug 11;44(31):590-1 [PMID: 7623762]
  48. J Clin Microbiol. 1995 Sep;33(9):2260-4 [PMID: 7494012]
  49. Clin Exp Immunol. 1995 Nov;102(2):438-42 [PMID: 7586703]
  50. Med Clin North Am. 1997 Jan;81(1):179-94 [PMID: 9012760]
  51. Vaccine. 1996 Dec;14(17-18):1620-6 [PMID: 9032890]
  52. Immunol Invest. 1997 Jan-Feb;26(1-2):117-28 [PMID: 9037617]
  53. Infect Immun. 1997 Mar;65(3):882-9 [PMID: 9038292]
  54. Infection. 1997 May-Jun;25(3):140-3 [PMID: 9181379]
  55. Clin Diagn Lab Immunol. 1995 Sep;2(5):609-15 [PMID: 8548542]
  56. Clin Immunol Immunopathol. 1996 May;79(2):105-14 [PMID: 8620616]
  57. J Mol Biol. 1996 May 24;258(5):747-62 [PMID: 8637007]
  58. Biol Chem. 1997 Jun;378(6):495-502 [PMID: 9224929]
  59. Clin Infect Dis. 1997 Jul;25 Suppl 1:S31-4 [PMID: 9233661]
  60. Ann Intern Med. 1997 Dec 15;127(12):1109-23 [PMID: 9412316]
  61. FEMS Immunol Med Microbiol. 1997 Oct;19(2):103-9 [PMID: 9395054]
  62. J Clin Microbiol. 1998 Feb;36(2):427-36 [PMID: 9466753]
  63. Clin Chem. 1998 Feb;44(2):232-8 [PMID: 9474017]
  64. An Med Interna. 1998 Jan;15(1):8-12 [PMID: 9580180]
  65. Postgrad Med. 1998 May;103(5):51-4, 57-9, 63-4 passim [PMID: 9590986]
  66. N Engl J Med. 1998 Jul 23;339(4):209-15 [PMID: 9673298]
  67. N Engl J Med. 1998 Jul 23;339(4):216-22 [PMID: 9673299]
  68. Clin Diagn Lab Immunol. 1998 Jul;5(4):456-62 [PMID: 9665948]
  69. Clin Diagn Lab Immunol. 1998 Jul;5(4):503-6 [PMID: 9665957]
  70. Vaccine. 1998 Oct;16(17):1688-92 [PMID: 9713948]
  71. J Immunol Methods. 1998 Jun 1;215(1-2):151-61 [PMID: 9744757]
  72. J Virol Methods. 1998 Aug;73(2):175-83 [PMID: 9766888]
  73. Nat Biotechnol. 1998 Nov;16(11):1068-73 [PMID: 9831038]
  74. J Clin Microbiol. 1999 Mar;37(3):548-52 [PMID: 9986810]
  75. Infection. 1999 May-Jun;27(3):177-82 [PMID: 10378128]
  76. JAMA. 1999 Jul 7;282(1):62-6 [PMID: 10404913]
  77. Eur J Clin Microbiol Infect Dis. 1999 Aug;18(8):551-60 [PMID: 10517192]
  78. J Clin Microbiol. 1999 Dec;37(12):3990-6 [PMID: 10565920]
  79. MMWR CDC Surveill Summ. 2000 Apr 28;49(3):1-11 [PMID: 10817483]
  80. Proc Natl Acad Sci U S A. 1975 Dec;72(12):4749-53 [PMID: 54916]

Grants

  1. R42 A141776/PHS HHS

MeSH Term

Amino Acid Sequence
Animals
Borrelia burgdorferi Group
Enzyme-Linked Immunosorbent Assay
Epitopes, B-Lymphocyte
Humans
Lyme Disease
Molecular Sequence Data
Peptide Library
Peptides

Chemicals

Epitopes, B-Lymphocyte
Peptide Library
Peptides

Word Cloud

Created with Highcharts 10.0.0LDpeptidespathogenseradiseasereactivitypatientsusedpeptideepitopespositivenegativewithoutproteinsdiagnosticSerumantibodiesLymeaffinityselect12largerandomlibrariesphagedisplayformatselectedsurveyedpanelsubjectsthusidentifying17diagnosticallyusefulbindingpattern:leastthreedefineeightsequencemotifsnonecanmatchedconvincinglysegmentsBorreliaburgdorferievidently"mimotopes"mimickingnaturalmatchingcontiguousaminoacidsPeptideslikebasisnewenzyme-linkedimmunosorbentassaysufficientspecificitysensitivityreplaceexpensiveimmunoblottingtestscurrentlyrequireddefinitiveserologicaldiagnosisMoreovermethoddiscoverrequireknowledgeinvolvedgenericproceduresapplicablealmostinfectiousincludingemergingdiseasesyetidentifiedIdentifyinglymeepitopediscovery

Similar Articles

Cited By