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 whole PLP molecule, with eight amino acid overlaps, were screened for their ability to induce experimental allergic encephalomyelitis in Biozzi AB/H (H-2dq1) mice. Clinical and histological evidence of experimental allergic encephalomyelitis developed after sensitization with native PLP and with the PLP sequence 56-70 (DYEYLINVIHAFQYV) but not with the other synthetic PLP peptides used. Nonobese diabetic mice that share similar MHC determinants (H-2Anod) with Biozzi AB/H mice, could be induced to develop experimental allergic encephalomyelitis after sensitization with either mouse spinal cord homogenate or the PLP 56-70 peptide. Although the PLP 56-70 overlaps with the encephalitogenic epitope of PLP (residues 43-64) in PL/J (H-2u) mice the Biozzi AB/H mice did not exhibit disease with either PLP 43-64 peptide or the nonapeptide PLP 56-64 that overlaps both the Biozzi AB/H and PL/J encephalitogenic peptides. The identification of a novel major encephalitogenic epitope of PLP for Biozzi AB/H mice, increases the repertoire of encephalitogenic epitopes of PLP and supports a role for PLP as a target Ag in autoimmune demyelinating diseases.