Calreticulin-Low-density lipoprotein receptor-related protein 1 complex (CRT-CD91 complex) (CRT-CD91 complex)

The Calreticulin-Low-density lipoprotein receptor-related protein 1 (CRT-CD91) complex is a pivotal molecular interaction that mediates the recognition and clearance of apoptotic or stressed cells by the innate immune system. Calreticulin, typically an endoplasmic reticulum-resident chaperone, translocates to the outer leaflet of the plasma membrane (ecto-CRT) in response to cellular stress or certain chemotherapeutic treatments, acting as a primary eat-me signal (Obeid et al., 2007, Nature Medicine). This surface-exposed calreticulin is specifically recognized by CD91 (also known as LRP1) on phagocytic cells like macrophages and dendritic cells (Gardai et al., 2005, Cell). The formation of the CRT-CD91 complex triggers the engulfment of the target cell and facilitates the processing and presentation of its antigens, a process central to Immunogenic Cell Death (ICD) (Kroemer et al., 2013, Annual Review of Immunology). In the context of oncology, the induction of this complex is a key mechanism for drugs like anthracyclines and oxaliplatin to stimulate a durable anti-tumor T-cell response. Conversely, the therapeutic blockade of don't eat me signals, such as CD47, is often used to enhance the pro-phagocytic activity of the CRT-CD91 axis in cancer immunotherapy. This complex also plays a role in maintaining self-tolerance, as defects in the clearance of apoptotic cells are associated with the development of autoimmune diseases like systemic lupus erythematosus.

Other names

CRT-CD91 complexCalreticulin-LRP1 complexEcto-calreticulin-CD91 interactionPro-phagocytic signal complexCalreticulin-Low-density lipoprotein receptor-related protein 1 interaction

Induction of immunogenic cell death (ICD) leads to the translocation of calreticulin to the cell surface, where it binds to the CD91 receptor on phagocytes to promote the engulfment of dying cells and the activation of an adaptive immune response.