The Formation of Antigenic Determinants

One of the questions which still requires clarification is whether covalent linkage is indeed necessary, although it is evident that it is sufficient for the establishment of antigenic determinants. This in turn raises the question why ionic and van der Waals bonds do not seem to suffice, although they are adequate for somewhat larger haptens, as discussed in Sect. C.III. 

A variety of biochemical pathways are known which may lead to reactive quinoid derivatives. They include dihydroxylation of aromatic or heterocyclic compounds and epoxide formation and hydrolysis to -diphenolic compounds (Booth and Boyland 1957) o- and p-hydroxylations of phenols or arylamines (In-SCOE et al. 1965 Miller et al. 1960 Booth and Boyland 1957) and rearrangement of -hydroxyarylamines to o-aminophenols (Miller and Miller 1960). It now appears that aromatic hydroxylations proceed via highly reactive arene oxides, i.e., compounds in which a formal aromatic double bond has undergone epoxidation. Depending on the compound, arene oxides may give rise to other electrophilic reactive species, including quinoid structures, but react as such readily with nucleophiles and thus provide a basis for understanding covalent attachment of aromatic hydrocarbon derivatives to protein and nucleic acids (Jerina and Daly 1974). 

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Investigations of the formation of antigenic and allergenic determinants of benzylpenicil-hn have identified a list of determinants that inclndes the penicUloyl, penidllenate, peni-cUloic acid, peniUoic acid, penamaldate, penicoyl, penicillanyl, and penicillamine stmctnres. 

The nature of the antigenic determinant has been characterized in a male worker with occupational asthma from nickel [415, 416] the antibody recognized Ni2+ bound at the natural Cu2 + /Ni2+ transport site of human albumin. The interpretation was deduced from metal ion blocking experiments and from the good agreement obtained between the pH dependency of the formation of the Ni2 + -albumin complex and the antigen-antibody complex. It was suggested that the antibody interaction depended on a special structural feature of the interaction of Ni2 + with human serum albumin, and perhaps the ability to form an octahedral complex affords one explanation [417]. 

When grown at 25°, mycelia, or conidia mixed with mycelia, produce di-O-rhamnosyl side-chains (see the preceding) that are the main, antigenic determinants, as shown by inhibition experiments with oligosaccharides and rabbit immune serum.131 The response of human sera to the polysaccharide, and the fact that 13C-n.m.r. spectroscopy showed that conidia of S. schenckii form a rhamnomannan similar to the yeast component and different from the di-O-rhamnosylman-nan of hyphae,132 suggest the formation of hyphae in vivo. 

The radioimmunoassay (RIA) for the determination of insulin developed by Yalow and Berson (1959) combined for the first time the high sensitivity of a ra-dioactively labeled compound with the high specificity of an immunological reaction by the formation of a thermodynamically stable antigen-antibody complex (dissociation constants are typically 10 9 -10 12 M). In this way it was possible to detect quantitatively substances in the attomolar range even in the presence... 

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