Synthetic copolymer 1 and myelin basic protein do not require processing prior to binding to class II major histocompatibility complex molecules on living antigen-presenting cells.
In the present study we attempted to examine whether copolymer 1 (Cop 1), a synthetic basic random copolymer of amino acids (a candidate drug for multiple sclerosis (MS)), and myelin basic protein (MBP) undergo processing prior to their binding to MHC class II molecules on antigen-presenting cells (APC). The direct binding of biotinylated Cop 1 and MBP to living APC was monitored by flow cytometry using phycoerythrin (PE)-streptavidin. The time course for either Cop 1 or MBP binding was similar at 37 degrees C and on ice. Both Cop 1 and MBP bound to glutaraldehyde-fixed APC. Furthermore, these biotinylated antigens bound also in the presence of protease inhibitors and lysosomotropic agents, suggesting that proteolysis is not required prior to their interaction with the MHC determinants. Finally, short fragments of Cop 1 molecule did not bind to most of the APC, suggesting that the polymeric nature of Cop 1 is important for its efficient and promiscuous binding.
Fridkis-Hareli
M
M
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Teitelbaum
D
D
Arnon
R
R
Sela
M
M
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D000068717:Glatiramer Acetate; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000188:drug therapy; D004676:Myelin Basic Protein / Q000276:immunology / Q000378:metabolism*; D010455:Peptides / Q000276:immunology / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects
D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D010455:Peptides; D011480:Protease Inhibitors; D000068717:Glatiramer Acetate