Fabfragment

Fabfragment refers to the fragment antigen-binding portion of an antibody. It is produced by proteolytic cleavage of a full immunoglobulin (such as an IgG) with enzymes like papain, which yields two Fab fragments and one Fc fragment. Each Fab contains the antigen-binding site formed by the variable regions of the heavy and light chains (VH and VL) together with the adjacent constant domains (CH1 and CL). The Fab fragment binds specific antigens through the complementarity-determining regions but lacks the Fc region that would engage Fc receptors or activate complement.

Structure and size notation: A Fab fragment is roughly 50 kilodaltons in size and consists of one light chain and one heavy-chain variable region paired with their respective constant domains, connected by disulfide bonds. In IgG digestion, two Fab fragments are produced per antibody, while the Fc fragment remains separate. A related product, the F(ab')2 fragment, arises from pepsin digestion and remains as a dimer of two Fab units linked by disulfide bonds, lacking the Fc portion.

Functions and uses: The absence of the Fc region means Fab fragments do not trigger Fc-mediated effector functions such as antibody-dependent cellular cytotoxicity or complement activation. They retain antigen-binding specificity and can offer improved tissue penetration due to their smaller size, making them useful in diagnostic assays and certain therapeutic contexts where Fc functions are undesirable. Examples include therapeutic Fab fragments like ranibizumab (anti-VEGF-A) and various diagnostic reagents.

Limitations and optimization: Fab fragments have shorter serum half-lives because they are cleared by the kidneys and do not benefit from FcRn recycling. To extend their half-life, they may be PEGylated or engineered for fusion to albumin-binding domains or other longer-lived formats.