Random three- and four-amino acid copolymers having lengths of 14-, 35-
and 50-amino acid residues are provided. Fifty-mers of FEAK were
effective inhibitors of MBP 85-99- or proteolipid protein (PLP)
40-60-specific HLA-DR-2-restricted T cell clones. These copolymers
efficiently suppressed the mouse disease EAE, which was induced in a
susceptible SJL/J (H-2.sup.S) strain of mice with either whole spinal
cord homogenate (WSCH) or with the encephalitogenic epitope PLP 139-151
(SEQ ID NO:4). YFAK 50-mer having a molar ratio of about Y 0.8:F 0.2
inhibited binding of biotinylated MBP 85-99 epitope to HLA-DR-2 molecules
more efficiently than either unlabeled MBP 85-99 or Copaxone.RTM.. YFAK
and FAK copolymers efficiently suppressed EAE induced in SJL/J
(H-2.sup.S) mice with the encephalitogenic epitope PLP 139-151.
Copolymers YFAK, VYAK and tryptophan-containing VWAK were efficacious in
alleviating severity and duration of symptoms of EAE induced by MBP 85-99
(SEQ ID NO:2), in a humanized mouse model expressing genes for both an
HLA-DR-2 linked to multiple sclerosis (MS) in humans and for a T cell
receptor from an MS patient.