Limited proteolysis of β2‐microglobulin at Lys‐58 by complement component C1s

Abstract

We have now demonstrated that activated complement component C1s cleaves β₂‐microglobulin at the position identical to that at which β₂‐microglobulin is cleaved in serum of patients suffering from lung cancer. The main cleavage is in the disulphide loop C‐terminal to Lys‐58, generating a modified form of β₂‐microglobulin with a two‐chain structure. The C‐terminal Lys‐58 in the A chain is highly susceptible to removal by a carboxypeptidase‐B‐like activity causing the formation of des‐Lys⁵⁸ ‐β₂‐microglobulin. This is the first demonstration of a non‐complement protein substrate for the proteolytic activity of C1s. The C1s‐induced cleavage of β₂‐microglobulin can be inhibited in the presence of C1 esterase inhibitor, demonstrating a regulatory function of C1 esterase inhibitor in the C1s‐induced cleavage of β₂‐microglobulin.