Differential tolerance is induced in T cells recognizing distinct epitopes of myelin basic protein.
Experimental allergic encephalomyelitis (EAE) is induced by T cell-mediated immunity to central nervous system antigens. In H-2u mice, EAE is mediated primarily by T cells specific for residues 1-11 of myelin basic protein (MBP). We demonstrate that differential tolerance to MBP1-11 versus epitopes in MBP121-150 is induced by expression of endogenous MBP, reflecting extreme differences in stability of peptide/MHC complexes. The diverse MBP121-150-specific TCR repertoire can be divided into three fine specificity groups. Two groups were identified in wild-type mice despite extensive tolerance, but the third group was not detected. Activated MBP121-150-specific T cells induce EAE in wild-type mice. Thus, encephalitogenic T cells that escape tolerance either recognize short-lived peptide/MHC complexes or express TCRs with unique specificities for stable complexes.
Harrington
C J
CJ
Department of Immunology, University of Washington, Seattle 98195, USA.
Paez
A
A
Hunkapiller
T
T
Mannikko
V
V
Brabb
T
T
Ahearn
M
M
Beeson
C
C
Goverman
J
J
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology; D006825:Hybridomas; D007108:Immune Tolerance / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D004676:Myelin Basic Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D007135:Immunoglobulin Variable Region; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta