AMELIORATION OF RELAPSING EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS WITH ALTERED MYELIN BASIC-PROTEIN PEPTIDES INVOLVES DIFFERENT CELLULAR MECHANISMS

T-cells specific for a region of human myelin basic protein, amino aci ds 87-99 (hMBP87-99), have been implicated in the development of multi ple sclerosis (MS) a demyelinating disease of the central nervous syst em. Administration of soluble altered peptide ligand (APL), made by su bstituting native residues with alanine at either positions 91(91K > A or A91) or 97 (97R > A or A97) in the hMBP87-99 peptide, blocked the development of chronic relapsing experimental autoimmune encephalomyel itis (R-EAE), in the SJL mouse. The non-encephalitogenic APL A91, appe ars to induce cytokine shifts from Th1 to Th2 in the target T-cells, w hereas the encephalitogenic superagonist APL A97 causes deletion of th e MBP87-99 responsive cells. Thus, single amino acid changes at differ ent positions in the same peptide epitope can lead to APL capable of c ontrolling auto-immune disease by different mechanisms.