Mast cell proteases liberate stable encephalitogenic fragments from intact myelin.
Protease-containing supernatants from activated rat mast cells were found to degrade purified rat myelin with a subsequent release of a stable encephalitogenic peptide. The two most abundant peptides were identified as residues 69-87 (GSLPQKSQRTQDENPVV) and residues 69-88 (GSLPQKSQRTQDENPVVH). While additional exposure to the mast cell supernatants removes the COOH terminal histamine from peptide 69-88 to yield peptide 69-87, additional proteolytic degradation of the 69-87 peptide was not detected. Immunization with this peptide emulsified in CFA caused the development of clinical experimental autoimmune encephalomyelitis (EAE) in Lewis rats. In addition this 69-87 sequence was found to activate resting encephalitogenic myelin basic protein-reactive T cell lines to adoptively transfer clinical EAE. The release of stable encephalitogenic peptides from the myelin sheath by mast cell proteases may play a role in activation of encephalitogen-specific T cells during the progression of EAE.
Dietsch
G N
GN
Immunology Research Laboratory, Veterans Affairs Medical Center, Portland, Oregon 97201.
Hinrichs
D J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology*; D010450:Endopeptidases / Q000502:physiology*; D016219:Immunotherapy, Adoptive; D008407:Mast Cells / Q000201:enzymology*; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology; D009186:Myelin Sheath / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
D004676:Myelin Basic Protein; D010446:Peptide Fragments; D010450:Endopeptidases