Dietsch G N, Hinrichs D J
Immunology Research Laboratory, Veterans Affairs Medical Center, Portland, Oregon 97201.
Cell Immunol. 1991 Jul;135(2):541-8. 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.
研究发现，活化大鼠肥大细胞含蛋白酶的上清液可降解纯化的大鼠髓磷脂，并随后释放出一种稳定的致脑炎性肽。两种含量最丰富的肽被鉴定为第69 - 87位氨基酸残基（GSLPQKSQRTQDENPVV）和第69 - 88位氨基酸残基（GSLPQKSQRTQDENPVVH）。虽然进一步暴露于肥大细胞上清液会使69 - 88肽的羧基末端组氨酸去除，从而产生69 - 87肽，但未检测到69 - 87肽的进一步蛋白水解降解。用在弗氏完全佐剂中乳化的该肽进行免疫，可使Lewis大鼠发生临床实验性自身免疫性脑脊髓炎（EAE）。此外，发现这个69 - 87序列可激活静息的致脑炎性髓鞘碱性蛋白反应性T细胞系，以过继转移临床EAE。肥大细胞蛋白酶从髓鞘中释放稳定的致脑炎性肽，可能在EAE进展过程中致脑炎性特异性T细胞的激活中起作用。
