Subtle effects on myelin basic protein-specific T cell responses can lead to a major reduction in disease susceptibility in experimental allergic encephalomyelitis

The presence of potentially autoreactive T cells is a necessary, but not su fficient, condition for the development of autoimmune disease. However, the relationship between T cell response and susceptibility to disease is not straightforward. In this report, we use experimental allergic encephalomyel itis as a model to demonstrate that subtle alterations of the T cell respon se to an encephalitogenic epitope are sufficient to cause a dramatic decrea se in disease susceptibility. Transgenic expression of a fusion protein of hen egg lysozyme and an encephalitogenic peptide of myelin basic protein (M BP) residues 84-105, coexpressed with MHC class II, causes profound toleran ce to hen egg lysozyme, while maintaining a near normal response to MBP, De tailed analysis of the T cell repertoire of transgenic animals using a pane l of T cell hybridomas revealed a highly selective loss of one minor compon ent of the response to the MBP84-104 region. Despite this, transgenic anima ls were highly resistant to experimental allergic encephalomyelitis inducti on with the MBP peptide, indicating that minor changes to the T cell repert oire may result in major alterations in disease susceptibility. Possible re asons for this are discussed.