Analysis of proteolipid protein (PLP)-specific T cells in multiple sclerosis: identification of PLP 95–116 as an HLA-DR2,w15-associated determinant

Abstract

Multiple sclerosis (MS) is a putative autoimmune disease that is linked with HLA-DR2,w15. Proteollpid protein (PLP) is a candidate autoantigen in MS, but the disease-associated epitopes have not been determined. Using overlapplng and non-overlapping PLP peptides, we have studied the T cell response to the major hydrophllic domain PLP 85–159 in the peripheral blood of MS and healthy subjects (HS). Short-term T cell lines (TCL) were selected against each peptide using microwell plates and the frequency of peptide-specific TCL was estimated. PLP 95–116-specific TCL were most efficiently generated and the frequency was significantly higher in MS compared with HS (P + and DR2,w15⁻ MS, TCL frequency to PLP 95–116 was significantly higher in DR2,w15⁺ MS (P+ MS (P< 0.025). Using DR gene-transfected L cells, we could show that the DRB1^*1501 product of the DR2 haplotype presents PLP 95–116 to TCL selected against the pepide. These results imply that PLP 95–116 represents a major epitope for the DR2,w15⁺MS.