Evidence that complement protein C1q interacts with C-reactive protein through its globular head region

Area of Science:

• Immunology
• Complement System Biology

Background:

• C1q initiates the classical complement pathway by binding to immune complexes and other ligands.
• The globular head regions (C1qGR) and collagen-like regions (C1qCLR) of C1q are implicated in ligand binding.
• C-reactive protein (CRP) is a known non-immunoglobulin ligand for C1q.

Purpose of the Study:

• To investigate the specific regions of C1q involved in the interaction with CRP and IgG.
• To determine whether C1q's globular head regions (C1qGR) or collagen-like regions (C1qCLR) mediate binding to CRP.

Main Methods:

• Utilized nine monoclonal antibodies (mAbs) against C1q: five targeting C1qGR and four targeting C1qCLR.
• Assessed the inhibitory effects of F(ab')(2) fragments of these mAbs on C1q binding to CRP and polymerized IgG.
• Measured the inhibition of C1 activation by CRP and polymerized IgG in vitro using the mAbs.

Main Results:

• Five mAbs against C1qGR successfully inhibited C1q binding to polymerized IgG.
• These same five mAbs also inhibited the interaction of C1q with CRP.
• Furthermore, these mAbs inhibited C1 activation by both CRP and polymerized IgG.
• No inhibition of C1q-CRP or C1q-IgG interaction, or complement activation, was observed with mAbs targeting C1qCLR.

Conclusions:

• The globular head regions (C1qGR) of C1q are crucial for the interaction with both CRP and IgG.
• The collagen-like regions (C1qCLR) of C1q are not involved in the physiological binding to CRP or IgG.
• These findings clarify the molecular interactions underlying complement activation by C1q ligands.