Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5400_Библиотеки_им_академика_М_И_Перельмана

identical κ or λ light chains and two γ heavy chains– connected by disulphide bonds and electrochemical interactions, reaching an approximately 150,000 Da molecular weight [6]. The fragment antigen binding (Fab) contains the complementarity determining regions (CDR) binding to the epitope on the target antigen. Monoclonal abs recognized only one epitope, and IgGs may bind to two epitopes simultaneously, since they comprise two Fab regions (Fig. 1). The fragment crystalline (Fc) is located on the heavy chains and is responsible for the effector functions of the Ab, through binding to either Fcγ receptors on immune cells (natural killer cells, macrophages, etc) or complement cascade enzymes (Fig. 2). Among IgG subclass, it is admitted that IgG1 and IgG3 display more potent effector mechanisms, as compared to IgG2 and IgG4, as they bind with different afinity to Fcγ receptors [7]. IgG1 and IgG3 also eficiently activate the classical route of complement, while IgG4 have limited complement activation and only under speciic conditions for IgG2. Finally, the Fc region also contains a highly conserved N-glycosylation site and the binding site to neonatal Fc receptor (FcRn), which is important for Ab pharmacokinetics (PK). Engineering Ab to sequentially replace murine sequence-derived amino acids with human ones (Fig. 1) has been done to signiicantly reduce immunogenicity [8, 9]. However, it remains unclear whether fully human Abs is less risky for immunogenicity than the humanized constructs. Some humanized and full-human Ab still carry immunogenicity risk.