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 ra ts with experimental autoimmune encephalomyelitis (EAE) was compared t o those eliciting in vitro antigen-specific T cell proliferation and a ugmentation of disease transfer. Utilizing a panel of synthetic peptid es with sequences representing the 68-86 region of guinea pig (GP-) or bovine myelin basic protein (B-MBP), animals were primed with one spe cies of peptide and subsequently challenged with either the same pepti de or peptides with truncations or substitutions representative of the other species of MBP. In regard to minimal length sequences capable o f eliciting delayed-type hypersensitivity (DTH), rats primed with GP-M BP and complete Freund's adjuvant (CFA) exhibited a hierarchical patte rn 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 reporte d for T cell proliferation and activation for disease transfer. Furthe rmore, a comparison of these T cell-mediated immune parameters, as eli cited by the substituted peptides, revealed the response patterns of D TH 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 cr oss-reactive pattern of recognition was observed in cells mediating di sease transfer, with all four 68-86 sequences capable of augmenting ac tivation for adoptive transfer of disease, regardless of the peptide s pecies for which the animal was primed. The differential antigen recog nition patterns observed for these EAE-associated immune responses sup ports the hypothesis that multiple T(H) cell subsets are involved in d isease pathogenesis.