DIRECT BINDING OF MYELIN BASIC-PROTEIN AND SYNTHETIC COPOLYMER-1 TO CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX-MOLECULES ON LIVING ANTIGEN-PRESENTING CELLS - SPECIFICITY AND PROMISCUITY

Copolymer 1 (Cop 1) is a synthetic basic random copolymer of amino aci ds that has been shown to be effective in suppression of experimental allergic encephalomyelitis and is being tested as a candidate drug for multiple sclerosis. It has been previously demonstrated that Cop 1 is immunologically cross-reactive with the autoantigen myelin basic prot ein (BP) and competitively inhibits the response to BP of T-cell lines and clones of different major histocompatibility complex (MHC) restri ctions, of both mouse and human origin. In the present study we demons trated the direct binding of Cop 1, using its biotinylated derivative, to MHC molecules on living antigen-presenting cells. Binding of bioti nylated BP and peptide p84-102 (an immunodominant epitope of BP) was a lso demonstrated. Cop 1 and BP bound in a promiscuous manner to differ ent types of antigen-presenting cells of various H-2 and HLA haplotype s. The specificity of the binding was confirmed by its inhibition with either the relevant anti-MHC class II antibodies or unlabeled analogs . Cop 1 exhibited the most extensive and fast binding to antigen-prese nting cells. In addition, Cop 1 inhibited the binding of biotinylated derivatives of BP and of p84-102 to the MHC class II molecules and eve n displaced these antigens when already bound. Thus, these results sug gest that Cop 1 indeed competes with BP for MHC binding and, thereby, inhibits T-cell responses to BP. The binding of Cop 1 to different DR alleles, probably because of its multiple MHC binding motifs, may indi cate its potential as a broad-spectrum drug for multiple sclerosis.