RECOGNITION OF THE IMMUNODOMINANT MYELIN BASIC-PROTEIN PEPTIDE BY AUTOANTIBODIES AND HLA-DR2-RESTRICTED T-CELL CLONES FROM MULTIPLE-SCLEROSIS PATIENTS - IDENTITY OF KEY CONTACT RESIDUES IN THE B-CELL AND T-CELL EPITOPES

Myelin basic protein (MBP) may be an important autoantigen in multiple sclerosis (MS), with the MBP(82-100) region being immunodominant for T cells and autoantibodies. The structural requirements for autoantibo dy recognition were compared to those previously defined for MBP-speci fic T cell clones, MBP autoantibodies were affinity-purified from cent ral nervous system lesions of 11/12 postmortem cases studied, The MBP( 83-97) peptide was immunodominant in all 11 cases since it inhibited a utoantibody binding to MBP > 95%, Residues contributing to autoantibod y binding were located in a 10-amino acid segment (V86-T95) that also contained the MHC/T cell receptor contact residues of the T cell epito pe, In the epitope center, the same residues were important for antibo dy binding and T cell recognition. Based on the antibody-binding moth, microbial peptides were identified that were bound by purified autoan tibodies. Autoantibody binding of microbial peptides required sequence identity at four or five contiguous residues in the epitope center. M icrobial peptides previously found to activate T cell clones did not h ave such obvious homology to MBP since sequence identity was not requi red at MHC contacts, The similar fine specificity of B cells and T cel ls may be useful for tolerance induction to MBP in MS.