Tolerance controls encephalitogenicity of alphaB-crystallin in the Lewis rat.
The myelin-associated protein, alphaB-crystallin, is considered a candidate autoantigen in multiple sclerosis (MS). In the present study, we examined the potential of alphaB-crystallin to induce experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Attempts to induce EAE with either bovine, rat or murine alphaB-crystallin or alphaB-crystallin peptides consistently failed. Immunization with either autologous rat or murine alphaB-crystallin did not trigger any antigen-specific T cell response. Immunization with bovine alphaB-crystallin or a synthetic peptide representing the cryptic epitope 49-64 did trigger T cell responses but these failed to crossreact with autologous rat alphaB-crystallin. Examination of lymphoid tissues of the Lewis rat revealed constitutive expression of alphaB-crystallin in thymus, spleen, and peripheral lymphocytes. Our data show that in Lewis rats, constitutive lymphoid expression of alphaB-crystallin is associated with a state of nonresponsiveness to autologous alphaB-crystallin that effectively controls the development of EAE in response to this myelin antigen.
van Stipdonk
M J
MJ
CLB, Sanquin Blood Supply Foundation, Department of Transplantation Immunology, Academical Medical Centre, University of Amsterdam, Netherlands. jm.vannoort@pg.tno.nl
Willems
A A
AA
Plomp
A C
AC
van Noort
J M
JM
Boog
C J
CJ
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D002417:Cattle; D003459:Crystallins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D009928:Organ Specificity; D010446:Peptide Fragments / Q000276:immunology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology
D001324:Autoantigens; D003459:Crystallins; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D012333:RNA, Messenger