ANALYSIS OF PROTEOLIPID PROTEIN (PLP)-SPECIFIC T-CELLS IN MULTIPLE-SCLEROSIS - IDENTIFICATION OF PLP-95-116 AS AN HLA-DR2,W15-ASSOCIATED DETERMINANT

Multiple sclerosis (MS) is a putative autoimmune disease that is linke d with HLA-DR2,w15. Proteolipid protein (PLP) is a candidate autoantig en in MS, but the disease-associated epitopes have not been determined , Using overlapping and non-overlapping PLP peptides, we have studied the T cell response to the major hydrophilic domain PLP 85-159 in the peripheral blood of MS and healthy subjects (HS), Short-term T cell li nes (TCL) were selected against each peptide using microwell plates an d the frequency of peptide-specific TCL was estimated, PLP 95-116-spec ific TCL were most efficiently generated and the frequency was signifi cantly higher in MS compared with HS (P < 0.05), When compared between DR2,w15(+) and DR2,w15(-) MS, TCL frequency to PLP 95-116 was signifi cantly higher in DR2,w15(+) MS (P < 0.005) and TCL reactive to the ove rlapping peptide 105-124 were also increased in DR2,w15(+) MS (P < 0.0 25), Using DR gene-transfected L cells, we could show that the DRB115 01 product of the DR2 haplotype presents PLP 95-116 to TCL selected ag ainst the peptide, These results imply that PLP 95-116 represents a ma jor epitope for the DR2,w15(+) MS.