Complement Receptor Type 1 (CR1)/CD35

Complement receptor type 1 (CR1), also known as CD35, is encoded by the CR1 gene and has a ~200 kDa molecular weight. The extracellular domain of the most common form of CR1 is made up of several 30 repeating units called short consensus repeats (SCRs). The SCRs are distributed in four long homologous repeats (LHRs A, B, C, and D), which is result from a seven-SCR unit. CR1 is mainly in neutrophils, monocytes, erythrocytes, B and T cells, and dendritic cells as well as in microglia, neurons, and the choroid plexus of the brain, in the membrane or insoluble form. The soluble CR1 (sCR1) form is derived from proteolytic cleavage in terminal secretory vesicles or the cell membrane.

Both CR1 forms play an important role in regulating complement activity which is achieved through binding cleaved C3b and C4b components and the complement cascade initiation molecules mannose-binding lectin (MBL-2), ficolins (FCN1, FCN2, and FCN3), and C1q. CR1 has the same binding site as serine proteases (MASPs) and competes with MASPs to prevent the initiation of the lectin pathway of complement. When the CR1 binding, the membrane-bound form of CR1 internalizes the opsonized elements or presents them to other immune cells, thus inhibiting the production of the C5 convertase and prevent the generation of the membrane attack complex (MAC). CR1 might also block excessive complement activation, playing as a cofactor for the Factor I-mediated cleavage of soluble/bound C3b and C4b.

Fig.1 Proposed role of CR1 polymorphisms of the Knop blood group and soluble CR1 in susceptibility to endemic pemphigus foliaceus. (Oliveira, 2019)

Reference

1. Oliveira, L. C., et al. Complement receptor 1 (CR1, CD35) polymorphisms and soluble CR1: A proposed anti-inflammatory role to quench the fire of “fogo selvagem” pemphigus foliaceus. Frontiers in immunology, 2019, 10, 2585.