After reading about complement pathway and the complement components, I was wondering, does the C1q component attach to the Fab fragment or to the Fc fragment? The pictures in Janeway's Immunobiology are confusing and the text don't mention about this.
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3$\begingroup$ You said Fab fragment twice. $\endgroup$– canadianerJan 4, 2015 at 5:41
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$\begingroup$ Can you please edit your question for clarity? Right now it is unclear what you're asking. $\endgroup$– anongoodnurseJan 4, 2015 at 6:37
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$\begingroup$ I think voting for question closure based on a typo is a bit harsh. If journal referees would start rejecting manuscripts on that basis even Nature would have trouble filling its pages =) $\endgroup$– AliceD ♦Jan 5, 2015 at 1:11
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1$\begingroup$ @ChrisStronks While I agree about the closing - an article in a bad grammatical style or with too much typos will never reach the reviewers. It will be sorted out by the editors when they do an initial review. $\endgroup$– Chris ♦Jan 5, 2015 at 8:34
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1 Answer
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Complement factor c1q binds to the constant Fc portion of an antibody (Duncan & Winter, 1988). Indeed, the constant (Fc) tail of the antibody is where other proteins involved in immune responses typically bind, most notably the Fc receptors (e.g., Clynes et al., 2000) found on immune cells such as B lymphocytes. Fc receptors mediate the recruitment of immune cells to a site of infection. The primary role of the Fab region is antigen binding as it contains the highly variable antigen binding domain. See the following figure (from the site of Invivogen) for the Fab and Fc region showing the constant and variable regions of antibodies:
Figure legend from Invivogen): The Fc region mediates effector functions, such as antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). In ADCC, the Fc region of an antibody binds to Fc receptors (FcγRs) on the surface of immune effector cells such as natural killers and macrophages, leading to the phagocytosis or lysis of the targeted cells. In CDC, the antibodies kill the targeted cells by triggering the complement cascade at the cell surface. I
The constant regions of antibodies are located on the heavy chain (CH1,2,3) and the light chain (CL). These constant regions are potential binding sites for other immune molecules as they are constant between antibodies, irrespective of the variable region in Fab. Most of the constant regions are found on the Fc region explaining its major role in binding other molecules involved in the immune response, including complement factor c1q. However, the constant regions in Fab (CL) may also provide binding sites for other proteins and indeed some bacterial compounds are known to bind to this region (Bouvet, 1994). However, I have not found evidence of c1q binding the Fab region.
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$\begingroup$ So Fab fragments can't activate the complement? $\endgroup$– TanMathJan 5, 2015 at 20:26
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