Skip to main content

Immunogenicity in Peptide-Immunotherapy: From Self/Nonself to Similar/Dissimilar Sequences

  • Chapter
Multichain Immune Recognition Receptor Signaling

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 640))

Abstract

The nature of the relationship between an antigenic amino acid sequence and its capability to evoke an immune response is still an unsolved problem. Although experiments indicate that specific (dis)continuous amino acid sequences may determine specific immune responses, how immunogenic properties and recognition informations are mapped onto a non-linear sequence is not understood.

Immunology has invoked the concept of self/nonself discrimination in order to explain the capability of the organism to selectively immunoreact. However, no clear, logical and rational pathway has emerged to relate a structure and its immuno-nonreactivity. It cannot yet be dismissed what Koshland wrote in 1990: “Of all the mysteries of modern science, the mechanism of self versus nonself recognition in the immune system ranks at or near the top.”1

This chapter reviews the concept of self/nonself discrimination in the immune system starting from the historical perspective and the conceptual framework that underlie immune reaction pattern. It also introduces future research directions based on a proteomic dissection of the immune unit, qualitatively defined as a low-similarity sequence and quantitatively delimitated by the minimum amino acid requisite able to evoke an immune response, independently of any, microbial or viral, “foreignness”.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Koshland DJ Jr. Recognizing self from nonself. Science 1990; 248:4961.

    Google Scholar 

  2. Gjertsen MK, Bakka A, Breivik J et al. Vaccination with mutant ras peptides and induction of T-cell responsiveness in pancreatic carcinoma patients carrying the corresponding RAS mutation. Lancet 1995; 346:1399–400.

    Article  PubMed  CAS  Google Scholar 

  3. Noguchi M, Kobayashi K, Suetsugu N et al. Induction of cellular and humoral immune responses to tumor cells and peptides in HLA-A24 positive hormone-refractory prostate cancer patients by peptide vaccination. Prostate 2003; 57:80–92.

    Article  PubMed  CAS  Google Scholar 

  4. Moulton HM, Yoshihara PH, Mason DH et al. Active specific immunotherapy with a beta-human chorionic gonadotropin peptide vaccine in patients with metastatic colorectal cancer: Antibody response is associated with improved survival. Clin Cancer Res 2002; 8:2044–2051.

    PubMed  CAS  Google Scholar 

  5. Offher H, Vandenbark AA. Congruent effects of estrogen and T-cell receptor peptide therapy on regulatory T-cells in EAE and MS. Int Rev Immunol 2005; 24:447–477.

    Article  CAS  Google Scholar 

  6. Herrington DA, Clyde DF, Losonsky G et al. Safety and immunogenicity in man of a synthetic peptide malaria vaccine against Plasmodium falciparum sporozoites. Nature 1987; 328:257–259.

    Article  PubMed  CAS  Google Scholar 

  7. El Kasmi KC, Muller CP. New strategies for closing the gap of measles susceptibility in infants: Towards vaccines compatible with current vaccination schedules. Vaccine 2001; 19:2238–2244.

    Article  PubMed  CAS  Google Scholar 

  8. Sabhanini L, Manocha M, Sridcvi K et al. Developing subunit inmiunogens using B-and T-cell epitopes and their constructs derived from Fl antigen of Yersinia pestis using novel delivery vehicles. FEMS Immunol Med Microbiol 2003; 1579:1–15.

    Google Scholar 

  9. Wiens GD, Pascho R, Winton JR. A single Ala139-to-Glu substitution in the Renibacterium salmoni-narum virulence-associated protein p57 results in antigenic variation and is associated with enhanced p57 binding to chinook salmon leukocytes. Appl Environ Microbiol 2002; 68:3969–3977.

    Article  PubMed  CAS  Google Scholar 

  10. Stephen CW, Helminen P, Lane DP. Characterisation of epitopes on human p53 using phage-displayed peptide libraries: Insights into antibody-peptide interactions. J Mol Biol 1995; 248:58–78.

    Article  PubMed  CAS  Google Scholar 

  11. van Regenmortel MHV. The recognition of proteins and peptides by antibodies. J Immunoassay 2000; 21:85–108.

    Article  PubMed  Google Scholar 

  12. van Regenmortel MHV. Antigenicity and immunogenicity of synthetic peptides. Biologicals 2001; 29:209–213.

    Article  PubMed  CAS  Google Scholar 

  13. Kellenberger C, Porciero S, Roussel A. Expression, refolding, crystallization and preliminary crystal-lographic study of MHC H-2K(k) complexed with octapeptides and non-apeptides. Acta Crystallogr D Biol Crystallogr 2004; 60:1278–1280.

    Article  PubMed  CAS  Google Scholar 

  14. Webb AI, Borg NA, Dimstone MA et al. The structure of H-2K(b) and K(bm8) complexed to a Herpes Simplex virus determinant: evidence for a conformational switch that governs T-cell repertoire selection and viral resistance. J Immunol 2004; 173:402–409.

    PubMed  CAS  Google Scholar 

  15. Bankovich AJ, Garcia KC. Not just any T-cell receptor will do. Immunity 2003; 18:7–11.

    Article  PubMed  CAS  Google Scholar 

  16. Garcia KC, Adams EJ. How the T-cell receptor sees antigen—A structural view. Cell 2005; 122:333–336.

    Article  PubMed  CAS  Google Scholar 

  17. Tauber AI. The biological notion of self and nonself In: Zalta EN, ed. The Stanford Encyclopedia of Philosophy. Spring 2006 Edition, (http://plato.stanford.edu/archives/spr2006/entries/biology-self/).

  18. Tauber AI. Moving beyond the immune self? Semin Immunol 2000; 12:241–248.

    Article  PubMed  CAS  Google Scholar 

  19. Silverstein AM, Rose NR. On the mystique of the immunological self. Immunol Rev 1997; 159:197–206.

    Article  PubMed  CAS  Google Scholar 

  20. Tauber AI, Chernyak L. Metchnikoff and the origins of immunology: From metaphor to theory. Oxford: Oxford University Press, 1991.

    Google Scholar 

  21. Mitchison NA, Katz DR, Chain B. Self/nonself discrimination among immunoregulatory (CD4) T-cells. Semin Immunol 2000; 12:179–183.

    Article  PubMed  CAS  Google Scholar 

  22. Matzinger P. Tolerance, danger and the extended family. Annu Rev Immunol 1994; 12:991–1045.

    PubMed  CAS  Google Scholar 

  23. Cohn M, Langman RE. The protecton: The evolutionarily selected unit of humoral immunity. Immunol Rev 1990; 115:1–131.

    Article  Google Scholar 

  24. Burnet FM, Fenner F. The Production of Antibodies, 2nd edition. Melbourne: Macmillan and Co., 1949;1–142.

    Google Scholar 

  25. Burnet FM. The concept of immunological surveillance. Prog Exp Tumor Res 1970; 13:1–27

    PubMed  CAS  Google Scholar 

  26. Medzhitov R, Janeway CA Jr. Decoding the patterns of self and nonself by the innate immune system. Science 2002; 296:298–300.

    Article  PubMed  CAS  Google Scholar 

  27. Natarajan K, Dimasi N, Wang J et al. Structure and function of natural killer cell receptors: multiple molecular solutions to self, nonself discrimination. Annu Rev Immunol 2002; 20:853–885.

    Article  PubMed  CAS  Google Scholar 

  28. Hickman HD, Luis AD, Buchli R et al. Toward a definition of self: Proteomic evaluation of the class I peptide repertoire. J Immunol 2004; 172:2944–2952.

    PubMed  CAS  Google Scholar 

  29. Matzinger P. The Danger model: A renewed sense of self. Science 296; 2002:301–305.

    Google Scholar 

  30. Crist E, Tauber AI. The phagocyte, the antibody and agency: Contending turn-of-the-century approaches to immunity. In: Moulin AM, Cambrosio A, eds. Singular Selves: Historical Issues and Contemporary Debates in Immunology. Amsterdam: Elsevier, 2001:115–139.

    Google Scholar 

  31. Fujinami RS, Oldstone MB, Wroblewska Z et al. Molecular mimicry in virus infection: Crossreaction of measles virus phosphoprotein or of herpes simplex virus protein with human intermediate filaments. Proc Natl Acad Sci USA 1983; 80:2346–2350.

    Article  PubMed  CAS  Google Scholar 

  32. Fourneau JM, Bach JM, van Endert PM et al. The elusive case for a role of mimicry in autoimmune diseases. Mol Immunol 2004; 40:1095–1102.

    Article  PubMed  CAS  Google Scholar 

  33. Van Bilsen JH, Wagenaar-Hilbers JP, Boot EP et al. Searching for the cartilage-associated mimicry epitope in adjuvant arthritis. Autoimmunity 2002; 35:201–210.

    Google Scholar 

  34. McDonald M, Currie BJ, Carapetis JR. Acute rheumatic fever: A chink in the chain that links the heart to the throat? Lancet Infect Dis 2004; 4:240–245.

    Article  PubMed  Google Scholar 

  35. Dinkla K, Rohde M, Jansen WT et al. Rheumatic fever-associated Streptococcus pyogenes isolates aggregate collagen. J Clin Invest 2003; 111:1905–1912.

    PubMed  CAS  Google Scholar 

  36. Guilherme L, Cunha-Neto E, Coelho V et al. Human heart-infiltrating T-cell clones from rheumatic heart disease patients recognize both streptococcal and cardiac proteins. Circulation 1995; 92:415–420.

    PubMed  CAS  Google Scholar 

  37. Panoutsakopoulou V, Sanchirico ME, Huster KM et al. Analysis of the relationship between viral infection and autoimmune disease. Immunity 2001; 15:137–147.

    Article  PubMed  CAS  Google Scholar 

  38. Kim KS, Hufnagel G, Chapman NM et al. The group B coxsackieviruses and myocarditis. Rev Med Virol 2001; 11:355–368.

    Article  PubMed  CAS  Google Scholar 

  39. Girones N, Cuervo H, Fresno M. Trypanosoma cruzi-induced molecular mimicry and Chagas' disease. Curr Top Microbiol Immunol 2005; 296:89–123.

    Article  PubMed  CAS  Google Scholar 

  40. Katz-Levy Y, Neville KL, Girvin AM et al. Endogenous presentation of self myelin epitopes by CNS-resident APCs in Theiler’s virus-infected mice. J Clin Invest 1999; 104:599–610.

    Article  PubMed  CAS  Google Scholar 

  41. Kuchroo VK, Anderson AC, Waldner H et al. T-cell response in experimental autoimmune encephalomyelitis (EAE): role of self and cross-reactive antigens in shaping, tuning and regulating the autopathogenic T-cell repertoire. Annu Rev Immunol 2002; 20:101–123.

    Article  PubMed  CAS  Google Scholar 

  42. Carrizosa AM, Nicholson LB, Farzan M et al. Expansion by self antigen is necessary for the induction of experimental autoimmune encephalomyelitis by T-cells primed with a cross-reactive environmental antigen. J Immunol 1998; 161:3307–3314.

    PubMed  CAS  Google Scholar 

  43. Lang HL, Jacobsen H, Ikemizu S et al. A functional and structural basis for TCR cross-reactivity in multiple sclerosis. Nat Immunol 2002; 3:940–943.

    Article  PubMed  CAS  Google Scholar 

  44. Miller SD, Vanderlugt CL, Begolka WSet al. Persistent infection with Theiler’s virus leads to CNS autoimmunity via epitope spreading. Nat Med 1997; 3:1133–1136.

    Article  PubMed  CAS  Google Scholar 

  45. Salazar CA, Rothemich M, Drouin EE et al. Human Lyme arthritis and the immunoglobulin G antibody response to the 37-kilodalton arthritis-related protein of Borrelia burgdorferi. Infect Immun 2005; 73:2951–2957.

    Article  PubMed  CAS  Google Scholar 

  46. Raveche ES, Schutzer SE, Fernandes H et al. Evidence of Borrelia autoimmunity-induced component of Lyme carditis and arthritis. J Clin Microbiol 2005; 43:850–856.

    Article  PubMed  CAS  Google Scholar 

  47. Atkinson MA, Bowman MA, Campbell L et al. Cellular immunity to a determinant common to glutamate decarboxylase and Coxsackie virus in insulin-dependent diabetes. J Clin Invest 1994; 94:2125–2129.

    Article  PubMed  CAS  Google Scholar 

  48. Bach JM, Otto H, Jung G et al. Identification of mimicry peptides based on sequential motifs of epitopes derived from 65-kDa glutamic acid decarboxylase. Eur J Immunol 1998; 28:1902–1910.

    Article  PubMed  CAS  Google Scholar 

  49. Hiemstra HS, Schloot NC, van Veelen PA et al. Cytomegalovirus in autoimmunity: T-cell crossreactivity to viral antigen and autoantigen glutamic acid decarboxylase. Proc Natl Acad Sci USA 2001; 98:3988–3991.

    Google Scholar 

  50. Horwitz MS, Bradley LM, Harbertson J et al. Diabetes induced by Coxsackie virus: initiation by bystander damage and not molecular mimicry. Nat Med 1998; 4:781–785.

    Article  PubMed  CAS  Google Scholar 

  51. Schloot NC, Willemen SJ, Duinkerken G et al. Molecular mimicry in type 1 diabetes mellitus revisited: T-cell clones to GAD65 peptides with sequence homology to Coxsackie or proinsulin peptides do not crossreact with homologous counterpart. Hum Immunol 2001; 62:299–309.

    Article  PubMed  CAS  Google Scholar 

  52. Uemura Y, Senju S, Maenaka K et al. Systematic analysis of the combinatorial nature of epitopes recognized by TCR leads to identification of mimicry epitopes for glutamic acid decarboxylase 65-specific TCRs. J Immunol 2003; 170:947–960.

    PubMed  CAS  Google Scholar 

  53. Benoist C, Mathis D. Autoimmunity provoked by infection: How good is the case for T-cell epitope mimicry? Nat Immunol 2001; 2:797–801.

    Article  PubMed  CAS  Google Scholar 

  54. Benjamin R, Parham P. Guilt by association: HLA-B27 and ankylosing spondylitis. Immunol Today 1990; 11:137–142.

    Article  PubMed  CAS  Google Scholar 

  55. Willers J, Lucchese A, Kanduc D et al. Molecular mimicry of phage displayed peptides mimicking GD3 ganglioside. Peptides 1999; 20:1021–1026.

    Article  PubMed  CAS  Google Scholar 

  56. Natale C, Giannini T, Lucchese A et al. Computer-assisted analysis of molecular mimicry between HPV16 E7 oncoprotein and human protein sequences. Immunol Cell Biol 2000; 78:580–585.

    Article  PubMed  CAS  Google Scholar 

  57. Kanduc D. Peptimmunology: immunogenic peptides and sequence redundancy. Curr Drug Discov Technol 2005; 2:239–244.

    Article  PubMed  CAS  Google Scholar 

  58. Kanduc D. Defining peptide sequences: from antigenicity to immunogenicity through redundancy. Curr Pharmacogenomics 2006; 4:33–37.

    Article  CAS  Google Scholar 

  59. Burnet FM. The Clonal Selection Theory of Acquired Immunity. Cambridge University Press, Cambridge: 1959; 1–209.

    Google Scholar 

  60. Burnet FM. Self and Not-Self Cambridge University Press, Cambridge: 1969; 1–318.

    Google Scholar 

  61. Nossal GJ. How is tolerance generated? Ciba Foimd Symp 1987; 129:59–72.

    CAS  Google Scholar 

  62. Gonzalo JA, de Alboran IM, Kroemer G. Dissociation of autoaggression and self-superantigen reactivity. Scand J Immunol 1993; 37:1–6.

    Article  PubMed  CAS  Google Scholar 

  63. Touma M, Mori KJ, Hosono M. Failure to remove autoreactive Vbeta6+ T-cells in Mls-1 newborn mice attributed to the delayed development of B-cells in the thymus. Immunology 2000; 100:424–431.

    Article  PubMed  CAS  Google Scholar 

  64. Mapara MY, Sykes M. Tolerance and cancer: Mechanisms of tumor evasion and strategies for breaking tolerance. J Clin Oncol 2004; 22:1136–1151.

    Article  PubMed  CAS  Google Scholar 

  65. May AC. Percent sequence identity; the need to be explicit. Structure 2004; 12:737–738.

    Article  PubMed  CAS  Google Scholar 

  66. Park J, Karplus K, Barrett C et al. Sequence comparisons using multiple sequences detect three times as many remote homologues as pairwise methods. J Mol Biol 1998; 284:1201–1210.

    Article  PubMed  CAS  Google Scholar 

  67. Lindner K, Mole SE, Lane DP et al. Epitope mapping of antibodies recognising the N-terminal domain of simian virus large tumour antigen. Intervirology 1998; 41:10–16.

    Article  PubMed  CAS  Google Scholar 

  68. Reddehase MJ, Rothbard JB, Koszinowski UH. A pentapeptide as minimal antigenic determinant for MHC class I-restricted T-lymphocytes. Nature 1989; 337:651–653.

    Article  PubMed  CAS  Google Scholar 

  69. Hemmer B, Kondo T, Gran B et al. Minimal peptide length requirements for CD4(+) T-cell clones-implications for molecular mimicry and T-cell survival. Int Immunol 2000; 12:375–383.

    Article  PubMed  CAS  Google Scholar 

  70. Wasniowska K, Petit-LeRoux Y, Toumamille C et al. Structural characterization of the epitope recognized by the new anti-Fy6 monoclonal antibody NaM 185-2C3. Transfus Med 2002; 12:205–211

    Article  PubMed  CAS  Google Scholar 

  71. Lu D, Kussie P, Pytowski B et al. Identification of the residues in the extracellular region of KDR important for interaction with vascular endothelial growth factor and neutralizing anti-KDR antibodies. J Biol Chem 2000; 275:14321–14330.

    Article  PubMed  CAS  Google Scholar 

  72. Kanduc D, Lucchese A, Mittelman A. Individuation of monoclonal anti-HPVI6 E7 antibody linear peptide epitope by computational biology. Peptides 2001; 22:1981–1985.

    Article  PubMed  CAS  Google Scholar 

  73. Mittelman A, Lucchese A, Sinha AA et al. Monoclonal and polyclonal humoral immune response to EC HER-2/neu peptides with low similarity to the hosts proteome. Int J Cancer 2002; 98:741–747.

    Article  PubMed  CAS  Google Scholar 

  74. Lucchese A, Stevanovic S, Sinha AA et al. Role of MHC II affinity and molecular mimicry in defining anti-HER-2/neu MAb-3 linear peptide epitope. Peptides 2003; 24:193–197.

    Article  PubMed  CAS  Google Scholar 

  75. Kanduc D, Fanizzi FP, Lucchese G et al. NMR probing of in silico identification of anti-HPVI6 E7 mAb linear peptide epitope. Peptides 2004; 25:243–250.

    Article  PubMed  CAS  Google Scholar 

  76. Mittelman A, Tiwari R, Lucchese G et al. Identification of monoclonal anti-HMW-MAA antibody linear peptide epitope by proteomic database mining. J Invest Dermat 2004; 123:670–675.

    Google Scholar 

  77. Dummer R, Mittelman A, Fanizzi FP et al. Nonself discrimination as a driving concept in the identification of an immunodominant HMW-MAA epitopic peptide sequence by autoantibodies from melanoma cancer patients. Int J Cancer 2004; 111:720–726.

    Article  PubMed  CAS  Google Scholar 

  78. Lucchese A, Mittelman A, Lin MS ct al. Epitope definition by proteomic similarity analysis: identification of the linear determinant of the anti-Dsg3 MAb 5H10. J Transl Med2004; 2:43.

    Article  PubMed  CAS  Google Scholar 

  79. Lucchese A, Willers J, Mittelman A et al. Proteomic scan for tyrosinase peptide antigenic pattern in vitiligo and melanoma. Role of sequence similarity and HLA-DRl affinity. J Immunol 2005; 175:7009–7020.

    PubMed  CAS  Google Scholar 

  80. Orlandi R, Formatici C, Menare S et al. X A linear region of a monoclonal antibody conformational epitope mapped on p185HER2 oncoprotein. Biol Chem 2005; 378:1387–1392.

    Article  Google Scholar 

  81. Sakakibara N, Kabeya H, Ohashi K et al. Epitope mapping of bovine leukemia virus transactivator protein tax. J Vet Med Sci 1998; 60:599–605.

    Article  PubMed  CAS  Google Scholar 

  82. Cardoso RM, Zwick MB, Stanfield RL et al. Broadly neutralizing anti-HIV antibody 4E10 recognizes a helical conformation of a highly conserved fusion-associated motif in gp41. Immunity 2005; 22:163–173.

    Article  PubMed  CAS  Google Scholar 

  83. Wilhamson P, Matthews R. Epitope mapping the Fim2 and Fim3 proteins of Bordetella pertussis with sera from patients infected with or vaccinated against whooping cough. FEMS Immunol Med Microbiol 1996; 13:69–78.

    Google Scholar 

  84. da Costa AV, Lafitte S, Fontaine J et al. Definition and mapping of epitopes recognized by specific monoclonal antibodies to Schistosoma bovis 28 kDa glutathione S-ransferase: Relation with anti-egg viability immunity. Parasite Immunol 1999; 21:9–18.

    Article  PubMed  CAS  Google Scholar 

  85. Larreta R, Guzman F, Patarroyo ME et al. Antigenic properties of the Leishmania infantum GRP94 and mapping of linear B-cell epitopes. Immunol Lett 2002; 80:199–205.

    Article  PubMed  CAS  Google Scholar 

  86. Lai MZ, Huang SY, Briner TJ et al. T-cell receptor gene usage in the response to lambda repressor cI protein. An apparent bias in the usage of a V alpha gene element. J Exp Med 1988; 168:1081–1097.

    Article  PubMed  CAS  Google Scholar 

  87. Shimonkevitz R, Colon S, Kappler JW et al. Antigen recognition by H-2-restricted T-cells. II. A tryptic ovalbumin peptide that substitutes for processed antigen. J Immunol 1984; 133:2067–2074.

    PubMed  CAS  Google Scholar 

  88. Pang LT, Kum WW, Chow AW. Inhibition of staphylococcal enterotoxin B-induced lymphocyte proliferation and tumor necrosis factor alpha secretion by MAb5, an anti-toxic shock syndrome toxin 1 monoclonal antibody. Infect Immun 2000; 68:3261–3268.

    Article  PubMed  CAS  Google Scholar 

  89. Burgess K, Han I, Zhang A et al. DiSSiMiL: Diverse Small Size Mini-Libraries applied to simple and rapid epitope mapping of a monoclonal antibody. J Pept Res 2001; 57:68–76.

    Article  PubMed  CAS  Google Scholar 

  90. Nastainczyk W, Issinger OG, Guerra B. Epitope analysis of the MAb 1AD9 antibody detection site in human protein kinase CK2alpha-subunit. Hybrid Hybridomics 2003; 22:87–90.

    Article  PubMed  CAS  Google Scholar 

  91. Perosa F, Luccarelli G, Prete M et al. Beta 2-microglobulin-free HLA class I heavy chain epitope mimicry by monoclonal antibody HC-10-specific peptide. J Immunol 2003; 171:1918–1926.

    PubMed  CAS  Google Scholar 

  92. Kerkar N, Choudhuri K, Ma Y et al. Cytochrome P4502D6(193-212): A new immunodominant epitope and target of virus/self cross-reactivity in liver kidney microsomal autoantibody type1-positive liver disease. J Immunol 2003; 170:1481–1489.

    PubMed  CAS  Google Scholar 

  93. Zhang XM, Liu G, Sun MJ. Epitopes of human brain acetylcholinesterase. Brain Res 2000; 868:157–164.

    Article  PubMed  CAS  Google Scholar 

  94. Deitiker P, Ashizawa T, Atassi MZ. Antigen mimicry in autoimmune disease. Can immune responses to microbial antigens that mimic acetylcholine receptor act as initial triggers of Myasthenia gravis? Hum Immunol 2000; 61:255–265.

    Article  PubMed  CAS  Google Scholar 

  95. He XL, Radu C, Sidney J et al. Structural snapshot of aberrant antigen presentation linked to autoimmunity: the immunodominant epitope of MBP complexed with I-Au. Immunity 2002; 17:83–94.

    Article  PubMed  CAS  Google Scholar 

  96. Crowe PD, Boehme SA, Wong T et al. Differential signaling and hierarchical response thresholds induced by an immunodominant peptide of myelin basic protein and an altered peptide ligand in human T-cells. Hum Immunol 1998; 59:679–689.

    Article  PubMed  CAS  Google Scholar 

  97. Dharmasaroja P. Specificity of autoantibodies to epitopes of myelin proteins in multiple sclerosis. J Neurol Sci 2003; 206:7–16.

    Article  PubMed  CAS  Google Scholar 

  98. Thrasyvoulides A, Sakarellos-Daitsiotis M, Philippou G et al. B-cell autoepitopes on the acetylcholin-esterase-homologous region of human thyroglobulin: Association with Graves’ disease and thyroid eye disease. Eur J Endocrinol 2001; 145:119–127.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Kanduc, D. (2008). Immunogenicity in Peptide-Immunotherapy: From Self/Nonself to Similar/Dissimilar Sequences. In: Sigalov, A.B. (eds) Multichain Immune Recognition Receptor Signaling. Advances in Experimental Medicine and Biology, vol 640. Springer, New York, NY. https://doi.org/10.1007/978-0-387-09789-3_15

Download citation

Publish with us

Policies and ethics