CD46 is composed of several domains, including four complement control protein (CCP) repeats, a serine/threonine-rich region, a transmembrane domain, and a cytoplasmic tail. The CCP repeats are essential for its regulatory function, as they serve as cofactors for the inactivation of complement components C3b and C4b by serum factor I . This inactivation prevents the deposition of complement on host tissues, thereby protecting cells from complement-mediated damage .
CD46 has a dual role in the immune system, participating in both innate and adaptive immunity. In the innate immune system, CD46 helps to modulate the activity of macrophages and dendritic cells by suppressing the production of interleukin-12 (IL-12), a pro-inflammatory cytokine . This modulation helps to prevent excessive inflammation and tissue damage.
In the adaptive immune system, CD46 plays a role in regulating T helper type 1 (Th1) immune responses. It influences the balance between the production of interferon-gamma (IFN-γ) and interleukin-10 (IL-10) within Th1 cells . This regulation is important for maintaining immune homeostasis and preventing autoimmune diseases.
The importance of CD46 in complement regulation is highlighted by the fact that genetic deficiencies in CD46 can lead to the development of atypical hemolytic-uremic syndrome (aHUS), a disease characterized by uncontrolled complement activation . Additionally, CD46 has been implicated in the development and progression of certain cancers .
Recombinant human CD46 is produced using various expression systems, such as HEK293 cells or E. coli, to ensure proper folding and post-translational modifications. The recombinant protein typically includes the extracellular domain of CD46 fused with a polyhistidine tag for purification purposes . The molecular weight of recombinant human CD46 is approximately 34 kDa, but due to glycosylation, it appears as a 55-60 kDa band in SDS-PAGE under reducing conditions .
Recombinant CD46 is used in research to study its role in the immune system, its interactions with pathogens, and its potential therapeutic applications. It is also used in the development of diagnostic assays and therapeutic interventions for diseases related to complement dysregulation .