mannan-binding lectin pathway (MLB pathway)

Function

• one of 3 pathways of complement activation
• uses mannose-binding lectin (MBL2) to activate the classical complement pathway independently of antibody
• MBL binds mannose & N-acetylglucosamine (Ca+2-dependent) expressed on the surface of certain pathogens, including acapsular gram-positive & gram-negative bacteria, mycobacteria, viruses, yeast, parasites & protozoa
• upon recognition of antigen, MBL2 adopts a conformational change that leads to activation of serine proteases MASP1 & MASP2
• after activation, MASP2 cleaves C4 to generate the classical C3 convertase C4b2a
• MASP1 has the ability to cleave C3 suggesting it might activate the complement alternative pathway directly
• following generation of the classical C3 convertase C4b2a by the MLB2-MASP1-MASP2 complex, complement activation occurs as in the classical complement cascade with possible activation of the complement alternative pathway
• the mannan-binding lectin pathway is regulated by C1 inhibitor & alpha-2 macroglobulin

Pathology

• specific antigen antibody complexes can activate the mannan-binding lectin pathway
• IgG that lack terminal galactose residues IgG-G0 found in plasma of patients with rheumatoid arthritis & other disorders interact in MLB2 & activate the mannan-binding lectin pathway
• defects in mannan-binding lectin pathway increase susceptibility to infection by Neisseria

More general terms

• biochemistry