Antigen binding site

The antigen-binding site is formed by close association of the hypervariable regions from both heavy and light chains... 

The variable domains associate in a strikingly different manner. It is obvious from Figure 15.11 that if they were associated in the same way as the constant domains, via the four-stranded p sheets, the CDR loops, which are linked mainly to the five-stranded p sheet, would be too far apart on the outside of each domain to contribute jointly to the antigen-binding site. Thus in the variable domains the five-stranded p sheets form the domain-domain interaction area (Figure 15.11). Furthermore, the relative orientation of the p strands in the two domains is closer to parallel than in the constant domains and the curvature of the five-stranded p sheets is such that they do not pack... 

The antigen-binding site binds haptens in crevices and protein antigens on large flat surfaces... 

Figure 15.19 Schematic representation of the peptide-binding domain of a class I MHC protein. The al and a2 domains are viewed from the top of the molecule, showing the empty antigen-binding site as well as the surface that is contacted by a T-cell receptor. (Adapted from P.J. Bjdrkman et al.. Nature 329 506-512, 1987.)...

Segal, D.M., et al. The three-dimensional structure of a phosphorylcholine-binding mouse immunoglobulin Fab and the nature of the antigen-binding site. Proc. Natl. Acad. Sci. USA 71 4298-4302, 1974. 

Another method to confirm that the peptide is specific is to test for specific inhibition of the binding of the antibody to its native protein target (i.e., in a tissue section) using soluble peptide. This tests whether the peptide was binding at or very close to the antigen binding site on an antibody. For each of the peptides described in this chapter, there was specific inhibition by soluble peptide but not by other, antigenically irrelevant peptides.6,7... 

Laman ID, Kors N, Heeney JL, et al. Fixation of cryo-sections under HIV-1 inactivating conditions integrity of antigen binding sites and cell surface antigens. Histochemistry 1991 96 177-183. 

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