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Tolerance controls encephalitogenicity of αB-crystallin in the Lewis rat

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Author: Stipdonk, M.J.B. van · Willems, A.A. · Plomp, A.C. · Noort, J.M. van · Boog, C.J.P.
Type:article
Date:2000
Institution: TNO Preventie en Gezondheid
Source:Journal of Neuroimmunology, 2, 103, 103-111
Identifier: 235422
doi: doi:10.1016/S0165-5728(99)00171-X
Keywords: Health · Tolerance · Autoantigen · Crystallin · Myelin · Myelin associated glycoprotein · Allergic encephalomyelitis · Animal cell · Animal experiment · Autoimmune disease · Central nervous system · Controlled study · Immunization · Lymphocyte proliferation · Multiple sclerosis · Nonhuman · Rat strain · T lymphocyte · Animals · Autoantigens · Cattle · Crystallins · Dose-Response Relationship, Immunologic · Encephalomyelitis, Autoimmune, Experimental · Hypersensitivity, Delayed · Immune Tolerance · Immunity, Cellular · Immunodominant Epitopes · Lymphoid Tissue · Male · Mice · Organ Specificity · Peptide Fragments · Phosphorylation · Rats · Rats, Inbred Lew · Reverse Transcriptase Polymerase Chain Reaction · RNA, Messenger · Species Specificity · T-Lymphocytes

Abstract

The myelin-associated protein, αB-crystallin, is considered a candidate autoantigen in multiple sclerosis (MS). In the present study, we examined the potential of αB-crystallin to induce experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Attempts to induce EAE with either bovine, rat or murine αB-crystallin or αB-crystallin peptides consistently failed. Immunization with either autologous rat or murine αB-crystallin did not trigger any antigen-specific T cell response. Immunization with bovine αB-crystallin or a synthetic peptide representing the cryptic epitope 49-64 did trigger T cell responses but these failed to crossreact with autologous rat αB-crystallin. Examination of lymphoid tissues of the Lewis rat revealed constitutive expression of αB-crystallin in thymus, spleen, and peripheral lymphocytes. Our data show that in Lewis rats, constitutive lymphoid expression of αB-crystallin is associated with a state of nonresponsiveness to autologous αB-crystallin that effectively controls the development of EAE in response to this myelin antigen. Copyright (C) 2000 Elsevier Science B.V. Chemicals/CAS: Autoantigens; Crystallins; Immunodominant Epitopes; Peptide Fragments; RNA, Messenger