PLP (178-191): NTWTTCQSIAFPSK  mouse,rat

Identification and characterization of a second encephalitogenic determinant of myelin proteolipid protein (residues 178-191) for SJL mice.

We previously described a synthetic peptide of myelin proteolipid protein (PLP),peptide 139-151,which induces experimental allergic encephalomyelitis in SJL/J (H-2s) mice. We have now identified an additional determinant,PLP residues 178-191,that is also a potent encephalitogen in this strain. When PLP peptide 178-191 was compared with peptide 139-151 on an equimolar basis,the day of onset of disease induced by PLP 178-191 was earlier,but the incidence,severity,and histologic features were indistinguishable. Lymph node cells from animals immunized with the whole PLP molecule responded to both PLP 178-191 and 139-151,suggesting immunologic codominance of the two epitopes. PLP 178-191 elicited stronger proliferative responses and this may relate to the earlier onset of disease induced with this peptide. Two CD4+,peptide-specific,I-A(s)-restricted T cell lines,selected by stimulation of lymph node cells with either PLP 178-191 or 139-151,were each encephalitogenic in naive syngeneic mice. The presence of multiple encephalitogenic codominant PLP epitopes within a single mouse strain emphasizes the complexity of the immune response to PLP and its potential as a target Ag in autoimmune demyelinating diseases.