Synthetic peptides that inhibit binding of the myelin basic protein 85-99 epitope to multiple sclerosis-associated HLA-DR2 molecules and MBP-specific T-cell responses.

Journal article

Copolymer 1 (Cop 1, poly [Y, E, A, K]) is a random synthetic amino acid copolymer effective in the treatment of relapsing forms of multiple sclerosis (MS), a disease that is linked to HLA-DR2 (DRB1*1501). In the present study various peptides, synthesized according to the binding motifs for both the immunodominant epitope of myelin basic protein (MBP) 85-99, a candidate autoantigen in MS, and Cop 1, differentially inhibited binding of these antigens to disease-associated HLA-DR2 (DRB1*1501) molecules. In particular, two peptides with residue K at position P-1, as referred to MBP 85-99, inhibited effectively the binding of both biotinylated MBP 85-99 and Cop 1 to HLA-DR2 molecules as well as IL-2 production by two MBP-specific HLA-DR2-restricted T-cell clones. These findings suggest the possible utility of these compounds or their more stable derivatives in treatment of MS.

Authors: Fridkis-Hareli, M; Stern, J; Fugger, L; Strominger, J

• Journal: Human immunology
• Volume: 62
• Issue: 8
• Pages: 753-763
• Publication date: 2001-08-01
• DOI: 10.1016/s0198-8859(01)00279-8
• EISSN: 1879-1166
• ISSN: 0198-8859
• Language: English
• Keywords: Dose-Response Relationship, Drug; Humans; T-Lymphocytes, Helper-Inducer; Peptides; Myelin Basic Proteins; HLA-DR2 Antigen; Antibodies; Peptide Fragments; Protein Binding; Cross Reactions; Immunodominant Epitopes; Multiple Sclerosis