Hypervariable amino acid sequence

Describe the features of the constant (C), variable (V), and hypervariable amino acid sequences of the L and H chains of IgG molecules. 

D. Davis, D. M. Stephens, C. Willers, P. J. Lachmann, Glycosylation governs the binding of antipeptide antibodies to regions of hypervariable amino acid sequence within recombinant gpl20 of human immunodeficiency virus type 1. J. Gen. Virol. 1990, 71, 2889-2898. 

In summary, for all the immunoglobulin molecules within one class, the amino acid sequence in the constant region of the chains is identical the massive number of different molecules within each class is accounted for by the amino acid sequences in the variable and hypervariable regions of both the light and heavy chains. 

To further reduce the immunogenicity of a chimeric antibody, researchers designed humanized antibodies that replace all mouse amino acid sequences except the hypervariable CDR domains of Ig that represent only a small fraction of the Fv fragment. Some humanized antibodies are now approved for clinical use and many more are being tested for an array of therapeutic indications (Tables 10.4 and 10.5). 

The amino acid sequence of the hypervariable loop is determined, and homology modelling then used to find a plausible secondary structure (Martin et al., 1989). 

A comparison of the amino acid sequences of different IgG antibodies from human beings or mice shows that the carboxyl-terminal half of the L chains and the carboxyl-terminal three-quarters of the H chains are very similar in all of the antibodies. Importantly, the amino-terminal domain of each chain is more variable, including three stretches of approximately 7 to 12 amino acids within each chain that are hypervariable, as shown for the H chain in Figure 33.10. The amino-terminal immunglobulin domain of each... 

---