The immune response to a subdominant epitope in myelin basic protein exon-2 results in immunity to intra- and intermolecular dominant epitopes.

Experimental autoimmune encephalomyelitis was induced in SJL/J mice by adoptive transfer of a MBP exon-2 peptide-specific T cell line. The T cell line, when tested for antigen specificity, reacted strongly with exon-2 peptide, but not with MBP peptides pAc1-11, p43-88, p89-101 or PLP p139-151. The specificity of splenic or lymph node T cells isolated from mice with acute or first relapse EAE induced by adoptive transfer of the exon-2-specific T cell line was identical to the transferred line. Splenocytes or lymphocytes isolated from mice at the second relapse were reactive with MBP p43-88, p89-101 and PLP p139-151 in addition to exon-2 peptide and MBP peptide Ac1-11. T cell lines selected by culture with MBP exon-2 peptide or PLP p139-151 from splenic cells from mice with relapsing EAE were weakly encephalitogenic; however, T cell lines selected from the same mice with MBP pAc1-11 were not encephalitogenic. T cells from the exon-2 and p139-151 T cell lines primed recipients for rapid onset severe EAE, whereas the pAc1-11 T cell line did not. T cells from the exon-2-specific line did not express V beta 17a+ TCR; however, peptide-specific T cell lines derived from the spleens of relapsing animals did express this TCR gene segment providing direct evidence of recruitment and sensitization of recipient T cells.