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.
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.
Fridkis-Hareli
M
M
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
Stern
J N
JN
Fugger
L
L
Strominger
J L
JL
D000906:Antibodies / Q000494:pharmacology; D003429:Cross Reactions; D004305:Dose-Response Relationship, Drug; D015802:HLA-DR2 Antigen / Q000378:metabolism*; D006801:Humans; D016056:Immunodominant Epitopes / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000276:immunology; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000906:Antibodies; D015802:HLA-DR2 Antigen; D016056:Immunodominant Epitopes; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D010455:Peptides; C107908:myelin basic protein 85-99; C021759:(T,G)-A-L