IDENTIFICATION OF A MAJOR ENCEPHALITOGENIC EPITOPE OF PROTEOLIPID PROTEIN (RESIDUES-56-70) FOR THE INDUCTION OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN BIOZZI-AB H AND NONOBESE DIABETIC MICE/

Native proteolipid (PLP) and synthetic 15- or 16-mer peptides of the w hole PLP molecule, with eight amino acid overlaps, were screened for t heir ability to induce experimental allergic encephalomyelitis in Bioz zi AB/H (H-2dq1) mice. Clinical and histological evidence of experimen tal allergic encephalomyelitis developed after sensitization with nati ve PLP and with the PLP sequence 56-70 (DYEYLINVIHAFQYV) but not with the other synthetic PLP peptides used. Nonobese diabetic mice that sha re similar MHC determinants (H-2A(nod)) with Biozzi AB/H mice, could b e induced to develop experimental allergic encephalomyelitis after sen sitization with either mouse spinal cord homogenate or the PLP 56-70 p eptide. Although the PLP 56-70 overlaps with the encephalitogenic epit ope of PLP (residues 43-64) in PL/J (H-2u) mice the Biozzi AB/H mice d id not exhibit disease with either PLP 43-64 peptide or the nonapeptid e PLP 56-64 that overlaps both the Biozzi AB/H and PL/J encephalitogen ic peptides. The identification of a novel major encephalitogenic epit ope of PLP for Biozzi AB/H mice, increases the repertoire of encephali togenic epitopes of PLP and supports a role for PLP as a target Ag in autoimmune demyelinating diseases.