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| SPREADING OF T-CELL AUTOIMMUNITY TO CRYPTIC DETERMINANTS OF AN AUTOANTIGEN |
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| Author(s): LEHMANN PV, FORSTHUBER T, MILLER A, SERCARZ EE |
| Source: NATURE Volume: 358 Issue: 6382 Pages: 155-157 Published: JUL 9 1992 |
| Times Cited: 836 References: 23 |
| Abstract: IMMUNIZATION with myelin basic protein (MBP) induces experimental allergic encephalomyelitis (EAE), a prototype of CD4+ T-cell mediated autoimmune disease. In rodents, MBP-reactive T-cell clones are specific for a single, dominant determinant on MBP and use a highly restricted number of T-cell receptor genes 1-3. Accordingly, EAE has been prevented by various receptor-specific treatments 1-8, suggesting similar strategies may be useful for therapy of human autoimmune disease. Here we report that in (SJL x B10.PL)F1 mice, immune dominance of a single determinant, MBP: Ac1-11, is confined to the inductive phase of EAE. In mice with chronic EAE, several additional determinants of MBP in peptides 35-47, 81-100 and 121-140 recall proliferative responses. Most importantly, reactivity to the latter determinants was also detected after induction of EAE with MBP peptide Ac1-11 alone; this demonstrates priming by endogenous MBP determinants. Thus, determinants of MBP that are cryptic 9-11 after primary immunization can become immunogenic in the course of EAE. Diversification of the autoreactive T-cell repertoire due to 'determinant spreading' has major implications for the pathogenesis of, and the therapeutic approach to, T-cell driven autoimmune disease. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV CALIF LOS ANGELES, DEPT MICROBIOL & MOLEC GENET, 405 HILGARD AVE, LOS ANGELES, CA 90024 USA |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: JC583 |
| ISSN: 0028-0836 |
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