Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen

Nature. 1992 Jul 9;358(6382):155-7. doi: 10.1038/358155a0.


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. Accordingly, EAE has been prevented by various receptor-specific treatments, 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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autoantigens / immunology*
  • Autoimmunity*
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Female
  • Guinea Pigs
  • Immune Tolerance
  • Immunization
  • Male
  • Mice
  • Molecular Sequence Data
  • Muramidase / immunology
  • Myelin Basic Protein / chemistry
  • Myelin Basic Protein / immunology*
  • T-Lymphocytes / immunology*


  • Autoantigens
  • Myelin Basic Protein
  • Muramidase