Half-molecules of IgG

Half-lives of IgG molecules of the various subclasses in normal individuals are shown in Table 3.1 (98). These are mean values based on rates of clearance of several I-labeled myeloma proteins. The rate of catabolism does not correlate with L chain type, Gm type, carbohydrate content, or net charge (99). The relatively short half-life of IgG3 may be related to its tendency to form aggregates (100) or to its large hinge region, which is a principal site of attack by proteolytic enzymes. 

Half-molecules of rabbit IgG, consisting of one complete H chain and one L chain, can be prepared by selective reduction of the H-H disulfide bond, followed by acidification. Half-molecules recombine spontaneously at neutral pH through strong noncovalent forces acting between the Fc segments of the two H chains therefore, they remain as half-molecules only under dissociating conditions, such as low pH or the presence of detergent (54,55-57). 

Evidence that half-molecules are univalent was obtained by an indirect procedure (55,57). When half-molecules of specifically purified rabbit antiovalbumin were allowed to recombine at neutral pH, a large fraction of the original precipitating activity was restored. If, however, the half-molecules of the antibody were mixed at low pH with a large excess of half-molecules of nonspecific IgG and then neutralized, the 7 S product specifically blocked the precipitin reaction of the antigen with untreated antiovalbumin, indicating the presence of univalent, hybrid molecules, each comprising a half-molecule of antibody and a halfmolecule of nonspecific IgG. 

The recombination of half-molecules of purified antibody with half-molecules of nonspecific IgG was studied quantitatively, using radioactive labels, and was found to be a random process (55). This was not unexpected since half-molecules are linked through noncovalent interactions in the Fc region, whose structure is independent of antibody specificity. The formation and mode of action of hybrid molecules is illustrated in Fig. 6.4. Hybrid molecules produced from Fab fragments are discussed in Chapter 8. 

When a mixture of half-molecules of rabbit IgG differing in allotype (at either the a or b locus) was allowed to reassemble, there was no pref-... 

Fig. 6.4. Mechanism of formation and mode of action of hybrid antibody molecules produced from half-molecules of rabbit IgG.

The single J chain in IgM (106) is disulfide bonded to the penultimate half-cystine residue of one, or possibly two /a chains (111,112). This would suggest an asymmetry in the IgM molecule, since a half-cystine linked to a J chain cannot also be part of an intrasubunit disulfide bond, and it is believed that most of the penultimate half-cystines do form such bonds this question requires further clarification. The L-H disulfide bonds in IgM involve half-cystine 140 in the H chain in this respect IgM is similar to molecules of the various subclasses of IgG, except for IgG 1 in which the L-H disulfide bond utilizes a half-cystine in the hinge region of the y chain. 

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