Mast cell proteases liberate stable encephalitogenic fragments from intact myelin

• Published in: Cellular immunology Vol. 135; no. 2; p. 541
• Main Authors: Dietsch, G N, Hinrichs, D J
• Format: Journal Article
• Language: English
• Published: Netherlands 01-07-1991
• Subjects: Amino Acid Sequence; Animals; Encephalomyelitis, Autoimmune, Experimental - etiology; Endopeptidases - physiology; Immunotherapy, Adoptive; Mast Cells - enzymology; Molecular Sequence Data; Myelin Basic Protein - immunology; Myelin Sheath - metabolism; Peptide Fragments - immunology; Peptide Fragments - metabolism; Rats; Rats, Inbred Lew
• ISSN: 0008-8749
• DOI: 10.1016/0008-8749(91)90297-O

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.