Convergent peptide libraries, or mixotopes, to elicit or to identify specific immune responses

Current Opinion in Immunology

Volumn 11, Issue 2, 1999, Pages 223-228

  Gras Masse, Hélène ^a   Georges, Bertrand ^a,b   Estaquier, Jérôme ^a,b   Tranchand Bunel, Denis ^a,b   Tartar, André ^d   Druilhe, Pierre ^c   Auriault, Claude ^a,b  

^a Laboratoire de Synthèse   (France)

^b INSTITUT PASTEUR DE LILLE   (France)

^c INSTITUT PASTEUR   (France)

^d NONE

Author keywords

[No Author keywords available]

Indexed keywords

ANTIGEN; EPITOPE; PEPTIDE LIBRARY;

ANTIGEN RECOGNITION; IMMUNE RESPONSE; MODEL; REVIEW;

EID: 0033118162     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0952-7915(99)80038-7     Document Type: Article

References (48)

1. Geysen HM, Meloen RH, Barteling SJ: Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid. Proc Natl Acad Sci USA 1984, 81:3998-4002.
2. Houghten RA: General method for the rapid solid-phase synthesis of large numbers of peptides: Specificity of antigen-antibody interaction at the level of individual amino acids. Proc Natl Acad Sci USA 1985, 82:5131-5135.
3. Devlin JJ, Panganiban LC, Devlin PE: Random peptide libraries: A source of specific protein binding molecules. Science 1990, 249:404-406.
4. Houghten RA, Pinilla C, Blondelle SE, Appel JR, Dooley CT, Cuervo JH: Generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery. Nature 1991, 354:84-86.
5. Pinilla C, Appel JR, Houghten RA: Investigation of antigen-antibody interactions using a soluble, non-support-bound synthetic decapeptide library composed of four trillion (4x10(12) sequences. Biochem J 1994, 301:847-853.
6. Hruby VJ, Ahn JM, Liao S: Synthesis of oligopeptide and peptidomimetic libraries. Curr Opin Chem Biol 1997, 1:114-119. This review presents recent advances in the field of oligopeptide and peptidomimetic libraries - including new synthetic methodologies, new analytical methods, new design methods and new assay procedures.
7. Scott JK, Smith GP: Searching for peptide ligands with an epitope library. Science 1990, 249:386-390.
8. Dooley CT, Chung NN, Schiller PW, Houghten RA: Acetalins: Opioid receptor antagonists determined through the use of synthetic peptide combinatorial libraries. Proc Natl Acad Sci USA 1993, 90:10811-10815.
9. Kupke T, Kempter C, Jung G, Gotz F: Oxidative decarboxylation of peptides catalyzed by flavoprotein EpiD. Determination of substrate specificity using peptide libraries and neutral loss mass spectrometry. J Biol Chem 1995, 270:11282-11289.
10. Geysen HM, Meloen RH, Barteling SJ: Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid. Proc Natl Acad Sci USA 1984, 81:3998-4002.
11. Geysen HM, Rodda SJ, Mason TJ: A priori delineation of a peptide which mimics a discontinuous antigenic determinant. Mol Immunol 1986, 23:709-715.
12. Lam KS, Lake D, Salmon SE, Smith J, Chen ML, Wade S, Abdul-Latif F, Knapp RJ, Leblova Z, Ferguson RD et al.: A one-bead one-peptide combinatorial library method for B-cell epitope mapping. Methods 1996, 9:482-493.
13. Daniels DA, Lane DP: Phage peptide libraries. Methods 1996, 9:494-507.
14. Tu J, Yu Z, Chu YH: Combinatorial search for diagnostic agents: Lyme antibody H9724 as an example. Clin Chem 1998, 44:232-238. This paper presents the identification from peptide libraries of ligands that bind tightly with disease-specific antibodies according to a strategy that should be applicable, at least in principle, to other ligand-receptor systems.
15. Slootstra JW, Puijk WC, Ligtvoet GJ, Kuperus D, Schaaper WM, Meloen RH: Screening of a small set of random peptides: A new strategy to identify synthetic peptides that mimic epitopes. J Mol Recognit 1997, 10:217-224.
16. Mattioli S, Imberti L, Stellini R, Primi D: Mimicry of the immunodominant conformation-dependent antigenic site of hepatitis A virus by motifs selected from synthetic peptide libraries. J Virol 1995, 69:5294-5299.
17. Lundin K, Samuelsson A, Jansson M, Hinkula J, Wahren B, Wigzell H, Persson MA: Peptides isolated from random peptide libraries on phage elicit a neutralizing anti-HIV-1 response: Analysis of immunological mimicry. Immunology 1996, 89:579-586.
18. Valadon P, Nussbaum G, Oh J, Scharff MD: Aspects of antigen mimicry revealed by immunization with a peptide mimetic of cryptococcus neoformans polysaccharide. J Immunol 1998, 161:1829-1836. This work describes peptide mimetics of polysaccharide epitopes in a model in which a crystal structure for a peptide-antibody complex is available; results suggest that the completeness of the fit in the binding site is an important driving force for mimicry.
19. Prezzi C, Nuzzo M, Meola A, Delmastro P, GAlfre G, Cortese R, Nicosia A, Monaci P, Angeletti P: Selection of antigenic and immunogenic mimics of hepatitis C virus using sera from patients. J Immunol 1996, 156:4504-4513.
20. Chargelegue D, Obeid OE, Hsu SC, Shaw MD, Denbury AN, Taylor G, Steward MW: A peptide mimic of a protective epitope of respiratory syncytial virus selected from a combinatorial library induces virus-neutralizing antibodies and reduces viral load in vivo. J Virol 1998, 72:2040-2046. This paper describes mimotopes of a conserved and conformationnally determined epitope, that did not bear any primary sequence relationship to sequences in the viral protein but possessed high affinity-constants with the monoclonal probe used for the screening. Presented as multiple antigenic peptides, these mimotopes induced virus-neutralizing antibodies.
21. Rudolf MP, Vogel M, Kricek F, Ruf C, Zurcher AW, Reuschel R, Auer M, Miescher S, Stadler BM: Epitope-specific antibody response to IgE by mimotope immunization. J Immunol 1998, 160:3315-3321. This work examines the possibility of using mimotope-derived peptides to induce anti-IgE response according to a strategy that is conceptually related to the anti-idiotype approach.
22. Van Regenmortel MH: Transcending the structuralist paradigm in immunology-affinity and biological activity rather than purely structural considerations should guide the design of synthetic peptide epitopes. Biomed Pept Proteins Nucleic Acids 1995, 1:109-116.
23. Udaka K, Wiesmuller KH, Kienle S, Jung G, Walden P: Decrypting the structure of major histocompatibility complex class I-restricted cytotoxic T lymphocyte epitopes with complex peptide libraries. J Exp Med 1995, 181:2097-2108.
24. Pridzun L, Wiesmuller KH, Kienle S, Jung G, Walden P: Amino acid preferences in the octapeptide subunit of the major histocompatibility complex class I heterotrimer H-2Ld. Eur J Biochem 1996, 236:249-253.
25. Fleckenstein B, Kalbacher H, Muller CP, Stoll D, Halder T, Jung G, Wiesmuller KH: New ligands binding to the human leukocyte antigen class II molecule DRB1 * 0101 based on the activity pattern of an undecapeptide library. Eur J Biochem 1996, 240:71-77.
26. Gundlach BR, Wiesmuller KH, Junt T, Kienle S, Jung G, Walden P: Determination of T cell epitopes with random peptide libraries. J Immunol Methods 1996, 192:149-155.
27. Gundlach BR, Wiesmuller KH, Junt T, Kienle S, Jung G, Walden P: Specificity and degeneracy of minor histocompatibility antigen-specific MHC-restricted CTL. J Immunol 1996, 156:3645-3651.
28. Valitutti S, Muller S, Cella M, Padovan E, Lanzavecchia A: Serial triggering of many T-cell receptors by a few peptide-MHC complexes. Nature 1995, 375:148-151.
29. Hudrisier D, Kessler B, Valitutti S, Horvath C, Cerottini JC, Luescher IF: The efficiency of antigen recognition by CD8+ CTL clones is determined by the frequency of serial TCR engagement. J Immunol 1998, 161:553-562. This work provides evidence that the functional CTL response correlated with the rate of dissociation of TCR-ligand complexes.
30. Hemmer B, Stefanova I, Vergelli M, Germain RN, Martin R: Relationships among TCR ligand potency, thresholds for effector function elicitation, and the quality of early signaling events in human T cells. J Immunol 1998, 160:5807-5814. The authors show that the absolute amount of each peptide required to stimulate the entire set of effector functions (potency) differs markedly among ligands for a single TCR - density, potency and quality of signaling all contribute in combination to the distinct effects of agonist ligands on T cell immunity - with several compensation mechanisms. As a result, high-affinity ligands will achieve similar degrees of functional activation (unlike ligands with low affinity).
31. Hemmer B, Vergelli M, Pinilla C, Houghten R, Martin R: Probing degeneracy in T-cell recognition using peptide combinatorial libraries. Immunol Today 1998, 19:163-168. This review discusses the degeneracy in T cell recognition and proposes a conceptual framework for lymphocyte selection and the occurence of autoimmunity.
32. Maddox J: Fuzzy sets make fuzzy logic. Nature 1983, 306:637.
33. + T cell clone that is specific for myelin basic protein peptides 86-96 was dissected by the response to a set of 220 11-mer peptide sublibraries; artificial peptides were found that induced proliferative responses at much lower concentrations than the autoantigen that was used to establish the clone.
34. Hemmer B, Vergelli M, Gran B, Ling N, Conlon P, Pinilla C, Houghten R, McFarland HF, Martin R: Predictable TCR antigen recognition based on peptide scans leads to the identification of agonist ligands with no sequence homology. J Immunol 1998, 160:3631-3636. This work provides evidence that ligands which do not share a single amino acid with the parent antigen can be identified that have comparable stimulatory potency for T cell clones.
35. Blake J, Johnston JV, Hellstrom KE, Marquardt H, Chen L: Use of combinatorial peptide libraries to construct functional mimics of tumor epitopes recognized by MHC class I-restricted cytolytic T lymphocytes. J Exp Med 1996, 184:121-130.
36. Gras-Masse H, Ameisen JC, Boutillon C, Rouaix F, Bossus M, Deprez B, Neyrinck JL, Capron A, Tartar A: Synthetic vaccines and HIV-1 hypervariability: A 'mixotope' approach. Pept Res 1992, 5:211-216.
37. Anderson DE, MAlley A, Benjamini E, Gardner MB, Torres JV: Hypervariable epitope constructs as a means of accounting for epitope variability. Vaccine 1994, 12:736-740.
38. Estaquier J, Gras-Masse H, Boutillon C, Ameisen JC, Capron A, Tartar A, Auriault C: The mixotope: A combinatorial peptide library as a T cell and B cell immunogen. Eur J Immunol 1994, 24:2789-2795.
39. Estaquier J, Boutillon C, Georges B, Ameisen JC, Tartar A, Auriault C: A combinatorial peptide library around variation of the human immunodeficiency virus (HIV-1) V3 domain leads to distinct T helper cell responses. J Pept Sci 1996, 2:165-175.
40. Estaquier J, Ameisen JC, Auriault C, Boutillon C, Gras-Masse H, Tartar A: Combinatorial peptide library as an immunogen. Methods Mol Biol 1998, 87:281-296. This provides a description of the methods used for the design, the synthesis and the biological evaluation of mixotopes.
41. Gras-Masse H, Boutillon C, Diesis E, Deprez B, Tartar A: Confronting the degeneracy of convergent combinatorial immunogens, or 'mixotopes', with the specificity of recognition of the target sequences. Vaccine 1997, 15:1568-1578. This study describes a series of eight mixotopes of increasing degeneracy that were designed from the natural variability of V3. Despite the extreme complexity of these immunogens, which evolved on a 13 log scale, most mixotopes elicited broadly specific antibodies which recognized different individual V3 sequences and the native gp120 protein. The results presented in this work suggest that cross-reactvity depends on the sequential similarity of the antigen to the parent immunogen.
42. Fidock DA, Sallenave-Sales S, Sherwood JA, Gachihi GS, Ferreira-da-Cruz MF, Thomas AW, Druilhe P: Conservation of the plasmodium falciparum sporozoite surface protein gene, STARP, in field isolates and distinct species of Plasmodium. Mol Biochem Parasitol 1994, 67:255-267.
43. Pasquetto V, Fidock DA, Gras-Masse H, Badell E, Eling W, Ballou WR, Belghiti J, Tartar A, Druilhe P: Plasmodium falciparum sporozoite invasion is inhibited by naturally acquired or experimentally induced polyclonal antibodies to the STARP antigen. Eur J Immunol 1997, 27:2502-2513. [Published erratum appears in Eur J Immunol 1997, 27:3084.] In these experiments, a repeat antigen of Plasmodium falciparum was chosen as a good candidate for the design of a mixotope because the considerable degeneracy of its repeat region creates a natural fuzzy set that could potentially be represented by such a preparation. This mixotope was sucessfully used as the antigen for the detection or the purification of functional antibodies from the sera of naturally infected humans. Comparison with a monovalent single-repeat peptide suggested that the mixotope may be more accurate than unique peptides in reflecting the true extent of polyclonal specificities to native antigens.
44. vanGrunsven WMJ, Nabbe A, Middeldorp JM: Identification and molecular characterization of two diagnostically relevant marker proteins of the Epstein-barr virus capsid antigen. J Med Virol 1993, 40:161-169.
45. vanGrunsven WMJ, Heerde EC, de Haard JW, Spaan WJM, Middeldorp JM: Gene mapping and expression of two immunodominant Epstein-barr virus capsid proteins. J Virol 1993, 67:3908-3916.
46. vanGrunsven WMJ, Spaan WJM, Middeldorp JM: Localization and diagnostic application of immunodominant domains of the BFRF3-encoded Epstein-Barr virus capsid protein. J Infect Dis 1994, 170:13-19.
47. Geysen HM, Mason TJ, Rodda SJ: Cognitive features of continuous antigenic determinants. J Mol Recog 1988, 1:32-41.
48. Tranchand-Bunel D, Auriault C, Diesis E, Gras-Masse H: Detection of human antibodies using 'convergent' combinatorial peptide libraries or 'mixotopes' designed from a non-variable antigen: Application to the EBV viral capsid antigen p18. J Pept Res 1998, 52:495-508. This paper provides evidence that mixotopes could be artificially designed from a nonvariable antigen and successfully used for the detection of human antibodies. This approach should be applicable to the discovery of novel diagnostic agents that could be especially interesting for the detection of antibodies that occur early in an immune response (IgA and IgM).