Selective cleavage of human IgG by the matrix metalloproteinases, matrilysin and stromelysin.

Abstract We have shown that two of the matrix metalloproteinases (MMPs), matrilysinand stromelysin-1, are capable of cleaving all of the human IgG subclasses. The cleavage occurs at a conserved site in the CH 2 domain of the heavy chain of IgG, releasing a single chain Fc-like fragment. We have not been able to demonstrate cleavage of IgA, IgD, IgM or IgE classes, which lack the cleavage site, nor could we show cleavage of IgG by collagenase, gelatinase, macrophage metalloelastase or membrane-type (MT)-MMP. This cleavage of IgG, by separating the antigen-binding (Fab′) 2 from the Fc portion, will remove much of the immunoglobulins' functionality, e.g. complement fixation, Fc receptorbinding. In the context of a tumour producing matrilysinor stromelysin, this may represent a way in which the tumour protects itself from ADCC. In inflammed or damaged tissues where plasma protein leakage occurs, degradation by MMPs may be a mechanism for clearance of IgG.