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 linked with HLA-DR2,w15. Proteolipid protein (PLP) is a candidate autoantigen 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 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 < 0.05). When compared between DR2,w15+ and DR2,w15- MS, TCL frequency to PLP 95-116 was significantly higher in DR2,w15+ MS (P < 0.005) and TCL reactive to the overlapping peptide 105-124 were also increased in DR2,w15+ 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 peptide. These results imply that PLP 95-116 represents a major epitope for the DR2,w15+ MS.
Ohashi
T
T
Department of Demyelinating Disease and Aging, National Institute of Neuroscience, Tokyo, Japan.
Yamamura
T
T
Inobe
J
J
Kondo
T
T
Kunishita
T
T
Tabira
T
T
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D000939:Epitopes / Q000032:analysis*; D005260:Female; D015802:HLA-DR2 Antigen / Q000032:analysis* / Q000235:genetics; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology*; D018991:Myelin Proteolipid Protein / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D010446:Peptide Fragments / Q000032:analysis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D015802:HLA-DR2 Antigen; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments