Autoimmune T cells: Immune recognition of normal and variant peptide epitopes and peptide-based therapy

Experimental autoimmune encephalomyelitis (EAE) results from T helper (T H) cell recognition of myelin basic protein (MBP). We have characterized T H cell reactivity in B10.PL and PL J (H-2 u) mice to 39 N-terminal MBP peptide derivatives of different lengths and with individual amino acid substitutions. The peptide determinant of murine MBP can be divided into a minimal stimulatory core region (residues 1–6) and a tail region (residues 7–20) that alters the structure of the core region to affect both T cell recognition and MHC binding. Core recognition by B10.PL and PL J mice is highly similar but in one case strain dependent. Peptide analogs that do not stimulate MBP-specific T H cells but bind to the I-A u molecule competitively inhibit T cell reactivity to MBP in vitro and prevent the induction of EAE in vivo.