Figure 2.

Complement activation in antibody-mediated rejection. Antibody-mediated rejection is caused by binding of antibodies to human leukocyte antigens (HLA) expressed on endothelial cells of the transplanted organ. The antibodies (referred to as donor specific antibodies, or DSA) activate the classical pathway of complement. Classical pathway activation causes the cleavage of C4, and one of the resultant C4 fragments (C4b) is covalently attached to target surfaces. C4b comprises part of the classical pathway C3 convertase, C4b2a. C3b can become covalently attached to target cells, similar to C4b. A protease called factor I (FI) controls complement activation by cleaving the C4b and C3b molecules, thereby stopping convertase activity. Although they are no longer catalytically active, the C4d and C3dg fragments remain bound to the target cells and can be detected by immunostaining of tissue biopsies.