Differential recognition of sequences within the encephalitogenic region of myelin basic protein capable of eliciting cell-mediated immune responses in experimental autoimmune encephalomyelitis

The fine specificity of myelin basic protein (MBP) epitopes capable of eliciting in vivo delayed-type hypersensitivity responses in Lewis rats with experimental autoimmune encephalomyelitis (EAE) was compared to those eliciting in vitro antigen-specific T cell proliferation and augmentation of disease transfer. Utilizing a panel of synthetic peptides with sequences representing the 68-86 region of guinea pig (GP-) or bovine myelin basic protein (B-MBP), animals were primed with one species of peptide and subsequently challenged with either the same peptide or peptides with truncations or substitutions representative of the other species of MBP. In regard to minimal length sequences capable of eliciting delayed-type hypersensitivity (DTH), rats primed with GP-MBP and complete Freund's adjuvant (CFA) exhibited a hierarchical pattern of responsiveness to challenge with a series of truncated peptides, ranking as follows: GP-68-86 > GP-72-86 > GP-68-84 > > GP-75-86 = no activity. This response pattern corresponds to that previously reported for T cell proliferation and activation for disease transfer. Furthermore, a comparison of these T cell-mediated immune parameters, as elicited by the substituted peptides, revealed the response patterns of DTH reactivity to be similar to that previously described for in vitro T cell proliferation with significant DTH responses generated only by the peptide species for which the animal was primed. In contrast, a cross-reactive pattern of recognition was observed in cells mediating disease transfer, with all four 68-86 sequences capable of augmenting activation for adoptive transfer of disease, regardless of the peptide species for which the animal was primed. The differential antigen recognition patterns observed for these EAE-associated immune responses supports the hypothesis that multiple T_H cell subsets are involved in disease pathogenesis.