Differential Tolerance Is Induced in T Cells Recognizing Distinct Epitopes of Myelin Basic Protein

• Published in: Immunity (Cambridge, Mass.) Mass.), 1998-05, Vol.8 (5), p.571-580
• Main Authors: Harrington, Cassie J, Paez, Angela, Hunkapiller, Tim, Mannikko, Valerie, Brabb, Thea, Ahearn, MaryEllen, Beeson, Craig, Goverman, Joan
• Format: Article
• Language: English
• Subjects: Animals; Encephalomyelitis, Autoimmune, Experimental - immunology; Epitope Mapping; Epitopes, T-Lymphocyte - immunology; H-2 Antigens - immunology; Hybridomas; Immune Tolerance - immunology; Immunoglobulin Variable Region - genetics; Mice; Mice, Inbred C3H; Myelin Basic Protein - immunology; Peptide Fragments - immunology; Receptors, Antigen, T-Cell, alpha-beta - genetics; Sequence Analysis, DNA; T-Lymphocytes - immunology
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(00)80562-2

Experimental allergic encephalomyelitis (EAE) is induced by T cell–mediated immunity to central nervous system antigens. In H-2 u 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.