International Immunology, Vol. 5, No. 9, pp. 1159-1165,September 1993
© 1993 Japanese Society for Immunology
Inhibition of experimental autoimmune encephalomyelitis by inhalation but not oral administration of the encephalitogenic peptide: influence of MHC binding affinity
Cambridge University Department of Pathology, Immunology Division Tennis Court Road, Cambridge CB2 1QP, UK
Correspondence to: Correspondence to: D. C. Wraith
This study explores antigen administration via mucosal surfaces as a potential means of inducing antigen-specific non-responsiveness in experimental autoimmune encephalomyelitis (EAE). In the H-2u mouse model of EAE, the acetylated N-termlnal peptide of myelin basic protein represents a dominant T cell epitope which on its own is sufficient to induce disease. Oral administration of the encephalitogenic peptide over a wide range of doses failed to induce oral tolerance to EAE. In marked contrast, a single intranasal dose of this peptide (Ac1–9 or Ac1–11) profoundly inhibited EAE when administered prior to disease induction. We investigated this phenomen further by using two analogues of Ac1–11 with alanlne or tyroslne at position 4 which display higher affinity binding to the I-Au molecule than the original peptide with lysine at this position. There was a positive correlation between the degree of protection from EAE and the affinity of individual peptides for class II MHC. Peptide inhalation inhibited not only EAE induced by subcutaneous injection of the encephalitogenic peptide but also disease induced by a complex mixture of potential auto-antigens such as spinal cord homogenate. Thus, in contrast to oral tolerance, nonresponsiveness by peptide inhalation is induclble with the encephalitogenic peptide in the absence of additional regulatory eprtopes. The finding that a single epitope may protect against EAE induced with whole spinal cord homogenate implies, however, that regulatory mechanisms affecting additional potential self-epltopes may play a significant role.
Keywords: antigen presentation, antigen-specific non-responsiveness, I-Au molecule, MHC class II, mucosal surfaces, oral tolerance, T cells
Received 15 March 1993, accepted 10 June 1992.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Gabrysova, K. S. Nicolson, H. B. Streeter, J. Verhagen, C. A. Sabatos-Peyton, D. J. Morgan, and D. C. Wraith Negative feedback control of the autoimmune response through antigen-induced differentiation of IL-10-secreting Th1 cells J. Exp. Med., August 3, 2009; 206(8): 1755 - 1767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kobayashi, N. Abiru, T. Arakawa, K. Fukushima, H. Zhou, E. Kawasaki, H. Yamasaki, E. Liu, D. Miao, F. S. Wong, et al. Altered B:9 23 Insulin, When Administered Intranasally with Cholera Toxin Adjuvant, Suppresses the Expression of Insulin Autoantibodies and Prevents Diabetes J. Immunol., August 15, 2007; 179(4): 2082 - 2088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. S. Lichtenegger, S. Kuerten, S. Faas, B. O. Boehm, M. Tary-Lehmann, and P. V. Lehmann Dissociation of Experimental Allergic Encephalomyelitis Protective Effect and Allergic Side Reactions in Tolerization with Neuroantigen J. Immunol., April 15, 2007; 178(8): 4749 - 4756. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Nicolson, E. J. O'Neill, A. Sundstedt, H. B. Streeter, S. Minaee, and D. C. Wraith Antigen-Induced IL-10+ Regulatory T Cells Are Independent of CD25+ Regulatory Cells for Their Growth, Differentiation, and Function J. Immunol., May 1, 2006; 176(9): 5329 - 5337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Hall, L. S. Cairns, D. M. Altmann, R. N. Barker, and S. J. Urbaniak Immune responses and tolerance to the RhD blood group protein in HLA-transgenic mice Blood, March 1, 2005; 105(5): 2175 - 2179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Harrison, M. C. Honeyman, C. E. Steele, N. L. Stone, E. Sarugeri, E. Bonifacio, J. J. Couper, and P. G. Colman Pancreatic {beta}-Cell Function and Immune Responses to Insulin After Administration of Intranasal Insulin to Humans At Risk for Type 1 Diabetes Diabetes Care, October 1, 2004; 27(10): 2348 - 2355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-R. Shen, A.-R. Youssef, A. Devine, L. Bowie, A. M. Hall, D. C. Wraith, C. J. Elson, and R. N. Barker Peptides containing a dominant T-cell epitope from red cell band 3 have in vivo immunomodulatory properties in NZB mice with autoimmune hemolytic anemia Blood, November 15, 2003; 102(10): 3800 - 3806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sundstedt, E. J. O'Neill, K. S. Nicolson, and D. C. Wraith Role for IL-10 in Suppression Mediated by Peptide-Induced Regulatory T Cells In Vivo J. Immunol., February 1, 2003; 170(3): 1240 - 1248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Y. Wu, F. J. Ward, and N. A. Staines Histone Peptide-Induced Nasal Tolerance: Suppression of Murine Lupus J. Immunol., July 15, 2002; 169(2): 1126 - 1134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Arneson, J. F. Katz, M. Liu, and A. J. Sant Hydrogen Bond Integrity Between MHC Class II Molecules and Bound Peptide Determines the Intracellular Fate of MHC Class II Molecules J. Immunol., December 15, 2001; 167(12): 6939 - 6946. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Jarnicki, T. Tsuji, and W. R. Thomas Inhibition of mucosal and systemic Th2-type immune responses by intranasal peptides containing a dominant T cell epitope of the allergen Der p 1 Int. Immunol., October 1, 2001; 13(10): 1223 - 1231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Quinn, M. Melo, D. Ethell, and Eli. E. Sercarz Relative resistance to nasally induced tolerance in non-obese diabetic mice but not other I-Ag7-expressing mouse strains Int. Immunol., October 1, 2001; 13(10): 1321 - 1333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Terui, K. Sano, H. Shirota, N. Kunikata, M. Ozawa, M. Okada, M. Honda, G. Tamura, and H. Tagami TGF-{beta}-Producing CD4+ Mediastinal Lymph Node Cells Obtained from Mice Tracheally Tolerized to Ovalbumin (OVA) Suppress Both Th1- and Th2-Induced Cutaneous Inflammatory Responses to OVA by Different Mechanisms J. Immunol., October 1, 2001; 167(7): 3661 - 3667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Slavin, R. Maron, and H. L. Weiner Mucosal administration of IL-10 enhances oral tolerance in autoimmune encephalomyelitis and diabetes Int. Immunol., June 1, 2001; 13(6): 825 - 833. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hänninen, A. Braakhuis, W. R. Heath, and L. C. Harrison Mucosal Antigen Primes Diabetogenic Cytotoxic T-Lymphocytes Regardless of Dose or Delivery Route Diabetes, April 1, 2001; 50(4): 771 - 775. [Abstract] [Full Text]
|
|
|
|
|
|
S. M. Anderton, C. G. Radu, P. A. Lowrey, E. S. Ward, and D. C. Wraith Negative Selection during the Peripheral Immune Response to Antigen J. Exp. Med., January 1, 2001; 193(1): 1 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-M. Stott, R. N. Barker, and S. J. Urbaniak Identification of alloreactive T-cell epitopes on the Rhesus D protein Blood, December 15, 2000; 96(13): 4011 - 4019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. G. Radu, S. M. Anderton, M. Firan, D. C. Wraith, and E. S. Ward Detection of autoreactive T cells in H-2u mice using peptide-MHC multimers Int. Immunol., November 1, 2000; 12(11): 1553 - 1560. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. F. HOYNE, K. TAN, M. CORSIN-JIMENEZ, K. WAHL, M. STEWART, S. E. M. HOWIE, and J. R. LAMB Immunological Tolerance to Inhaled Antigen Am. J. Respir. Crit. Care Med., October 1, 2000; 162(4): S169 - 174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. F. Hoyne, I. Le Roux, M. Corsin-Jimenez, K. Tan, J. Dunne, L. M. G. Forsyth, M. J. Dallman, M. J. Owen, D. Ish-Horowicz, and J. R. Lamb Serrate1-induced Notch signalling regulates the decision between immunity and tolerance made by peripheral CD4+ T cells Int. Immunol., February 1, 2000; 12(2): 177 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hirschberg, G. T. Layton, S. J. Harris, N. Savage, M. J. Dallman, and J. R. Lamb CD4+ T cells induced by virus-like particles expressing a major T cell epitope down-regulate IL-5 production in an ongoing immune response to Der p 1 independently of IFN-{gamma} production Int. Immunol., December 1, 1999; 11(12): 1927 - 1934. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Burkhart, G. Y. Liu, S. M. Anderton, B. Metzler, and D. C. Wraith Peptide-induced T cell regulation of experimental autoimmune encephalomyelitis: a role for IL-10 Int. Immunol., October 1, 1999; 11(10): 1625 - 1634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Grogan, A. Kramer, A. Nogai, L. Dong, M. Ohde, J. Schneider-Mergener, and T. Kamradt Cross-Reactivity of Myelin Basic Protein-Specific T Cells with Multiple Microbial Peptides: Experimental Autoimmune Encephalomyelitis Induction in TCR Transgenic Mice J. Immunol., October 1, 1999; 163(7): 3764 - 3770. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Haneda, K. Sano, G. Tamura, H. Shirota, Y. Ohkawara, T. Sato, S. Habu, and K. Shirato Transforming Growth Factor-beta Secreted from CD4+ T Cells Ameliorates Antigen-Induced Eosinophilic Inflammation . A Novel High-Dose Tolerance in the Trachea Am. J. Respir. Cell Mol. Biol., August 1, 1999; 21(2): 268 - 274. [Abstract] [Full Text]
|
|
|
|
|
|
E. M. Janssen, M. H. M. Wauben, E. H. Jonker, G. Hofman, W. Van Eden, F. P. Nijkamp, and A. J. M. Van Oosterhout Opposite Effects of Immunotherapy with Ovalbumin and the Immunodominant T-Cell Epitope on Airway Eosinophilia and Hyperresponsiveness in a Murine Model of Allergic Asthma Am. J. Respir. Cell Mol. Biol., July 1, 1999; 21(1): 21 - 29. [Abstract] [Full Text]
|
|
|
|
|
|
B. Metzler, C. Burkhart, and D. C. Wraith Phenotypic analysis of CTLA-4 and CD28 expression during transient peptide-induced T cell activation in vivo Int. Immunol., May 1, 1999; 11(5): 667 - 675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Laliotou and A. D Dick Modulating phenotype and cytokine production of leucocytic retinal infiltrate in experimental autoimmune uveoretinitis following intranasal tolerance induction with retinal antigens Br J Ophthalmol, April 1, 1999; 83(4): 478 - 485. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. I. Pearson, A. M. Gautam, I. C. Rulifson, R. S. Liblau, and H. O. McDevitt A small number of residues in the class II molecule I-Au confer the ability to bind the myelin basic protein peptide Ac1-11 PNAS, January 5, 1999; 96(1): 197 - 202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P GARSIDE, A M. MOWAT, and A KHORUTS Oral tolerance in disease Gut, January 1, 1999; 44(1): 137 - 142. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Porgador, H. F. Staats, Y. Itoh, and B. L. Kelsall Intranasal Immunization with Cytotoxic T-Lymphocyte Epitope Peptide and Mucosal Adjuvant Cholera Toxin: Selective Augmentation of Peptide-Presenting Dendritic Cells in Nasal Mucosa-Associated Lymphoid Tissue Infect. Immun., December 1, 1998; 66(12): 5876 - 5881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Anderton, S. P. Manickasingham, C. Burkhart, T. A. Luckcuck, S. J. Holland, A. G. Lamont, and D. C. Wraith Fine Specificity of the Myelin-Reactive T Cell Repertoire: Implications for TCR Antagonism in Autoimmunity J. Immunol., October 1, 1998; 161(7): 3357 - 3364. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Leadbetter, C. R. Bourque, B. Devaux, C. D. Olson, G. H. Sunshine, S. Hirani, B. P. Wallner, D. E. Smilek, and M. P. Happ Experimental Autoimmune Encephalomyelitis Induced with a Combination of Myelin Basic Protein and Myelin Oligodendrocyte Glycoprotein Is Ameliorated by Administration of a Single Myelin Basic Protein Peptide J. Immunol., July 1, 1998; 161(1): 504 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. N. Barker, A. M. Hall, G. R. Standen, J. Jones, and C. J. Elson Identification of T-Cell Epitopes on the Rhesus Polypeptides in Autoimmune Hemolytic Anemia Blood, October 1, 1997; 90(7): 2701 - 2715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Williams, L. M. Stasiuk, T. O. Nashar, C. M. Richards, A. K. Lang, M. J. Day, and T. R. Hirst Prevention of autoimmune disease due to lymphocyte modulation by the B-subunit of Escherichia coli heat-labile enterotoxin PNAS, May 13, 1997; 94(10): 5290 - 5295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Prakken, R. van der Zee, S. M. Anderton, P. J. S. van Kooten, W. Kuis, and W. van Eden Peptide-induced nasal tolerance for a mycobacterial heat shock protein 60 T cell epitope in rats suppresses both adjuvant arthritis and nonmicrobially induced experimental arthritis PNAS, April 1, 1997; 94(7): 3284 - 3289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.I. Pearson, W. van Ewijk, and H.O. McDevitt 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., February 17, 1997; 185(4): 583 - 600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Laliotou, J. Liversidge, J. V Forrester, and A. D Dick Interphotoreceptor retinoid binding protein is a potent tolerogen in Lewis rat: suppression of experimental autoimmune uveoretinitis is retinal antigen specific Br J Ophthalmol, January 1, 1997; 81(1): 61 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Harrison, M. Dempsey-Collier, D. R. Kramer, and K. Takahashi Aerosol Insulin Induces Regulatory CD8 {gamma}{delta} T Cells That Prevent Murine Insulin-dependent Diabetes J. Exp. Med., December 1, 1996; 184(6): 2167 - 2174. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Meeting Report and Proceedings: Multiple Sclerosis Society of Great Britain and Northern Ireland Multiple Sclerosis, August 1, 1996; 2(1): 1 - 55. [PDF]
|
|