Mehtap Cabus
Prof. Collins Jones
IgNAR Antibody Assignment
10.14.2014
IgNAR Antibodies
Antibodies (Ab) are proteins produced by plasma cells to identify and fight with foreign objects such as, viruses, bacteria, and parasites. They are also called immunoglobulins (Ig). IgA, IgD, IgE, IgG, and IgM are seen in human blood serum. Also, there are single-domain antibodies (sdAb), such as IgNAR (Immunoglobulin new antigen receptors) produced by sharks and camels. The differences between human antibodies and single-domain antibodies show that IgNAR has many advantages because of its properties.
In common antibodies, the antigen binding region consists of the variable domains of the heavy and light chains (VH and VL). Heavy-chain antibodies can bind antigens despite having only VH domains (Heavy-chain antibody, Wikipedia). Each chain contains one variable and three constant domains. IgA, IgD, IgE, IgG, and IgM can be examples for that feature. However, new antigen receptor (IgNAR) antibodies from sharks are disulphide bonded dimers of two protein chains, each containing one variable and five constant domains (Streltsov, Carmichael & Nuttall, 2005). Furthermore, there are three types of IgNAR, type 1, type 2, and type 3 (Streltsov, Carmichael & Nuttall, 2005). Figure 1 (Wikipedia)
Having 5 five constant domains (CH) per chain instead of three, containing several disulfide bonds in unusual positions, and forming an extension of CDR3 loop cause IgNAR to be more stable than conventional antibodies.
Figure 2 (Dooley, Helen)
Besides, in common antibodies, Fab (50 kDa) that contains VH and VL chains recognizes an immunogen. However, IgNAR molecules can be manipulated by molecular engineering to produce the variable domain of a single heavy chain polypeptide (vNARs) which able to recognize an immunogen has small size (15kDa) (Juarez et al, 2011).
Figure 3 (absoluteantibody.com)
Another advantage of IgNAR is the melting temperature. The melting temperature of the sdAb of shark is between 42°C and 77°C. They also showed superior heat stability, exhibiting slow loss of activity over the course of one hour at high temperature (95 degrees C), while conventional antibodies lost all activity in the first 5-10min (Liu et al, 2007).
Also, IgNAR contains an N-linked oligosaccharide attached to the second heavy-chain constant domain (CH2) that is essential for antibody effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytolysis (CDC), and for retaining a long serum half-life (Harmsen & Haard 2007).
As a summary, the shark antigen-binding V(NAR) domain has the potential to provide an attractive alternative to traditional biotherapeutics based on its small size, advantageous physiochemical properties, and unusual ability
