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Epitopes of myelin basic protein that trigger TGF-beta release after oral tolerization are distinct from encephalitogenic epitopes and mediate epitope-driven bystander suppression.
J Immunol 1993; 151(12):7307-15JI

Abstract

We have been studying the suppression of experimental autoimmune encephalomyelitis in the Lewis rat after oral administration of myelin basic protein (MBP). Suppression is mediated by CD8+ T cells that adoptively transfer protection and suppress immune responses in vitro. This suppression is mediated by secretion of TGF-beta following triggering by the fed antigen. In the present study, we tested the ability of overlapping 20 amino acid peptides from MBP to trigger suppression mediated by spleen cells from Lewis rats orally tolerized to MBP. Using a transwell system, we found that spleen cells from MBP orally tolerized animals stimulated by residues 21-40, 51-70 and 101-120 of MBP suppress proliferative responses of an ovalbumin specific cell line. This suppression correlated with secretion of TGF-beta by cells stimulated with the peptide. In addition, T cells from animals fed the tolerogenic peptide 21-40 alone secreted TGF-beta whereas no TGF-beta release or in vitro suppression was observed in animals fed the MBP encephalitogenic determinant 71-90. The 71-90 peptide triggered proliferation of MBP primed cells from animals immunized with MBP/CFA whereas the suppressor epitopes identified above did not. Furthermore, oral administration of peptide 21-40 suppressed disease induced by peptide 71-90. DTH responses to 71-90 were not affected by oral administration of peptide 21-40 whereas DTH responses to whole MBP were suppressed. These results demonstrate that distinct suppressor determinants exist on MBP which are separate from encephalitogenic determinants, and that epitope-driven bystander suppression plays an important role in down-regulation of tissue specific autoimmune processes following oral tolerization. These findings have important implications for the design of tissue specific targeted immunotherapy by oral tolerization in humans.

Authors+Show Affiliations

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7505026

Citation

Miller, A, et al. "Epitopes of Myelin Basic Protein That Trigger TGF-beta Release After Oral Tolerization Are Distinct From Encephalitogenic Epitopes and Mediate Epitope-driven Bystander Suppression." Journal of Immunology (Baltimore, Md. : 1950), vol. 151, no. 12, 1993, pp. 7307-15.
Miller A, al-Sabbagh A, Santos LM, et al. Epitopes of myelin basic protein that trigger TGF-beta release after oral tolerization are distinct from encephalitogenic epitopes and mediate epitope-driven bystander suppression. J Immunol. 1993;151(12):7307-15.
Miller, A., al-Sabbagh, A., Santos, L. M., Das, M. P., & Weiner, H. L. (1993). Epitopes of myelin basic protein that trigger TGF-beta release after oral tolerization are distinct from encephalitogenic epitopes and mediate epitope-driven bystander suppression. Journal of Immunology (Baltimore, Md. : 1950), 151(12), pp. 7307-15.
Miller A, et al. Epitopes of Myelin Basic Protein That Trigger TGF-beta Release After Oral Tolerization Are Distinct From Encephalitogenic Epitopes and Mediate Epitope-driven Bystander Suppression. J Immunol. 1993 Dec 15;151(12):7307-15. PubMed PMID: 7505026.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Epitopes of myelin basic protein that trigger TGF-beta release after oral tolerization are distinct from encephalitogenic epitopes and mediate epitope-driven bystander suppression. AU - Miller,A, AU - al-Sabbagh,A, AU - Santos,L M, AU - Das,M P, AU - Weiner,H L, PY - 1993/12/15/pubmed PY - 1993/12/15/medline PY - 1993/12/15/entrez SP - 7307 EP - 15 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 151 IS - 12 N2 - We have been studying the suppression of experimental autoimmune encephalomyelitis in the Lewis rat after oral administration of myelin basic protein (MBP). Suppression is mediated by CD8+ T cells that adoptively transfer protection and suppress immune responses in vitro. This suppression is mediated by secretion of TGF-beta following triggering by the fed antigen. In the present study, we tested the ability of overlapping 20 amino acid peptides from MBP to trigger suppression mediated by spleen cells from Lewis rats orally tolerized to MBP. Using a transwell system, we found that spleen cells from MBP orally tolerized animals stimulated by residues 21-40, 51-70 and 101-120 of MBP suppress proliferative responses of an ovalbumin specific cell line. This suppression correlated with secretion of TGF-beta by cells stimulated with the peptide. In addition, T cells from animals fed the tolerogenic peptide 21-40 alone secreted TGF-beta whereas no TGF-beta release or in vitro suppression was observed in animals fed the MBP encephalitogenic determinant 71-90. The 71-90 peptide triggered proliferation of MBP primed cells from animals immunized with MBP/CFA whereas the suppressor epitopes identified above did not. Furthermore, oral administration of peptide 21-40 suppressed disease induced by peptide 71-90. DTH responses to 71-90 were not affected by oral administration of peptide 21-40 whereas DTH responses to whole MBP were suppressed. These results demonstrate that distinct suppressor determinants exist on MBP which are separate from encephalitogenic determinants, and that epitope-driven bystander suppression plays an important role in down-regulation of tissue specific autoimmune processes following oral tolerization. These findings have important implications for the design of tissue specific targeted immunotherapy by oral tolerization in humans. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/7505026/Epitopes_of_myelin_basic_protein_that_trigger_TGF_beta_release_after_oral_tolerization_are_distinct_from_encephalitogenic_epitopes_and_mediate_epitope_driven_bystander_suppression_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=7505026 DB - PRIME DP - Unbound Medicine ER -