1. Binding motifs of copolymer 1 to multiple sclerosis- and rheumatoid arthritis-associated HLA-DR molecules.
- Author
-
Fridkis-Hareli M, Neveu JM, Robinson RA, Lane WS, Gauthier L, Wucherpfennig KW, Sela M, and Strominger JL
- Subjects
- Amino Acid Sequence, Amino Acids analysis, Aminopeptidases chemistry, Antibodies metabolism, Arthritis, Rheumatoid immunology, Binding Sites immunology, Binding Sites, Antibody, Chromatography, High Pressure Liquid, Glatiramer Acetate, HLA-DR Antigens immunology, HLA-DR1 Antigen metabolism, HLA-DR2 Antigen metabolism, HLA-DR4 Antigen metabolism, Humans, Multiple Sclerosis immunology, Peptide Fragments isolation & purification, Peptides isolation & purification, Polymers isolation & purification, Arthritis, Rheumatoid metabolism, HLA-DR Antigens metabolism, Multiple Sclerosis metabolism, Peptide Fragments immunology, Peptide Fragments metabolism, Peptides immunology, Peptides metabolism, Polymers metabolism, Saccharomyces cerevisiae Proteins
- Abstract
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). Cop 1 binds promiscuously, with high affinity and in a peptide-specific manner to purified MS-associated HLA-DR2 (DRB1*1501) and rheumatoid arthritis-associated HLA-DR1 (DRB1*0101) or HLA-DR4 (DRB1*0401) molecules. In the present work at least 95% of added Cop 1 could be bound to recombinant "empty" HLA-DR1 and -DR4, and 80% could be bound to HLA-DR2 proteins. Amino acid composition, HPLC profiles, and sequencing patterns of Cop 1 eluted by acid extraction from HLA-DR molecules were similar to those of the unseparated Cop 1. Protruding N-terminal ends of Cop 1 bound to HLA-DR1, -DR2, or -DR4 molecules were then treated with aminopeptidase I, followed by elution, HPLC, and pool sequencing. In contrast to untreated or unbound Cop 1, this material exhibited distinct motifs at some positions with increases in levels of E at the first and second cycles, of K at the second and third cycles, and of Y (presumably at P1 of the bound peptide) at the third to fifth cycles, regardless of the HLA-DR molecule employed. No preference was seen at the following cycles that were mainly A. These first pooled HLA-DR binding epitopes provide clues to the components of Cop 1 that are biologically active in suppressing MS and possibly rheumatoid arthritis.
- Published
- 1999