Antibody Structure
Basic Structure of Antibodies
Antibody molecules are roughly Y-shaped glycoproteins with a molecular weight of approximately 150 kDa. A typical IgG antibody has two copies of each of two polypeptide chains: the light chain (25 kDa) and the heavy chain (50 kDa). The disulfide bonds link two heavy chains to each other and each heavy chain to a light chain. These chains pair in such a way as to create three structural domains, two antigen-binding fragments (Fabs) and one crystallizable fragment (Fc), that are linked by a flexible “hinge” region. The antibody can be readily cleaved into Fab and Fc fragments by proteases. CH2 and CH3 comprise the Fc fragment, which can bind to cell surface receptors present on immune cell populations. The Fab fragment is a mixed light-heavy chain dimer of variable light (VL)-constant light (CL) paired with variable heavy (VH)-constant heavy 1 (CH1) segments. There are five types of Ig H chain (α, δ, ε, γ, and μ) and two types of Ig L chain (λ and κ) in mammals.
Fig 1. Structure of a monoclonal antibody. (Loureiro, 2015)
The Function of the Fragments
In any given antibody, the two H chains and the two L chains are identical, giving an antibody molecule two identical antigen-binding sites. This endows the antibody with the ability to bind to two identical antigens on a surface simultaneously, thereby increasing the strength of the interaction. Fabs contain antigen-binding sites. The Fc fragment is the part of the antibody molecule that does not interact with antigen, but rather interacts with effector molecules and cells, and it differs between H chain isotypes.
The Application of Fragments
In addition to the dominant full-length monoclonal antibodies, antibody engineering technologies have progressed in recent years to produce highly optimized therapies. Several engineered antibodies are as follows.
- Single-chain variable fragment antibody (scFv). scFv consists of variable domains of VH and VL chains joined by a peptide linker. scFv antibodies are the smallest immunoglobulins, but they have a high antigen-binding affinity. Compared with monoclonal antibodies, scFvs can access the intracellular region and bind to intracellular oncoantigens.
- Divalent and multivalent scFvs. Divalent scFvs were developed from the monovalent scFvs, either through the spontaneous non-covalent association of two scFv molecules (diabodies) or through the covalent disulfide bond. Divalent and multivalent scFvs were also generated by linking two or more scFv molecules using a peptide linker.
- Nanobodies, which are derived from the VHH domains of heavy-chain antibodies, are the smallest antigen-binding domains. This kind of antibody is also referred to as camelid single-domain antibody (sdAb).
- Heavy chain antibodies (HCAbs). Different from scFvs, HCAbs are small antibodies that are naturally devoid of light chains, the antigen-binding fragment of which consists of only one single domain referred to as sdAb (Nb) or the H chain antibody variable region (VHH).
Fig 2. Various genetically engineered antibody fragments. (Jain, 2007)
Creative Biolabs has built up a world-class ecosystem of expertise and capabilities to provide you a personalized solution to meet all your demands. We can provide various ViroAntibody products including a wide range of primary antibodies, secondary antibodies, isotype controls. If you are interested in our products, please feel free to contact us for more information.
References
- Loureiro, L.R.; et al. Challenges in antibody development against Tn and Sialyl-Tn antigens. Biomolecules. 2015, 5(3): 1783-809.
- Jain, M.; et al. Engineering antibodies for clinical applications. Trends Biotechnol. 2007, 25(7): 307-316.
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