Lack of "Determinant Spread" to the Minor Encephalitogenic Epitope in Myelin Basic Protein-Induced Acute Experimental Autoimmune Encephalomyelitis in the Rat

Acute and monophasic experimental autoimmune encephalomyelitis (EAE) was induced in rats by immunization with myelin basic protein (MBP). Proliferative responses of lymph node cells to major and minor encephalitogenic and nonencephalitogenic determinants of the MBP molecules were measured at various time intervals after the immunization. Results of these experiments revealed that additional responses to minor determinants which had been observed at the late stage of mouse EAE (Lehmann et al., Nature356, 155, 1992) were very weak and short-lived in the rat. Furthermore, the response to the minor encephalitogenic determinant was not recognized throughout the course of EAE. Coimmunization with synthetic peptides, corresponding to the major and minor determinants, induced T-cell response only to the major determinant. These findings suggest that poor generation of T cells reactive with the minor encephalitogenic epitope is attributable to peptide competition between these two determinants. The present results, together with those reported in mice, strongly suggest that differences in the clinical course of EAE, i.e., acute monophasic or chronic relapsing, is closely related to the presence or absence of "determinant spread" to minor encephalitogenic epitope(s).