The nature of the antigen-antibody complexes initiating the specific wheal-and-flare reaction in sensitized man.
To study the nature of the antigen-antibody complexes which initiate the specific wheal-and-flare (W & F) reaction in sensitized man, a homologous series of bivalent, oligovalent, and multivalent benzylpenicilloyl (BPO) haptens were quantitatively compared for their effectiveness in eliciting W & F in BPO-sensitized human subjects.A series of seven divalent haptens were capable of eliciting W & F, but these generally were not maximally effective elicitors. Of the divalent haptens, those with separation chains of 8 or 13 A were the most effective. Of the oligovalent haptens, maximal effectiveness was attained with BPO(6)-lysine(7), and not with BPO(2)-lysine(3) or BPO(4)-lysine(4), i.e., haptens which are 6- 3- and 4-valent, respectively, from a chemical point of view. However, evidence was obtained from quantitative precipitation experiments which indicated that BPO(6)-lysine(7) functions as a trivalent hapten immunologically, i.e., capable of binding three antibody molecules per mole hapten. Large molecularsized haptens with immunological valences of 7 or 12, but in which the haptenic groups were widely separated, were comparatively ineffective elicitors of W & F. In individual subjects, threshold W & F reactions were obtained with equimolar concentrations of the differently sized divalent, oligovalent, and multivalent haptens. The results demonstrate that for maximally effective elicitation of W & F by haptens, trivalency with optimal distances of separation of haptenic groups is necessary and sufficient. These results indicate the requirement for the formation of a high energy complex of two or three membrane-fixed skin-sensitizing antibody molecules closely bridged together by the elicitor hapten as the initiator of the W & F reaction.
D000328:Adult; D000368:Aged; D000818:Animals; D000906:Antibodies; D000937:Antigen-Antibody Reactions; D001665:Binding Sites; D002854:Chromatography, Paper; D003876:Dermatitis, Atopic / Q000139:chemically induced*; D004342:Drug Hypersensitivity; D005260:Female; D006241:Haptens / Q000494:pharmacology*; D006801:Humans; D008239:Lysine; D008297:Male; D008875:Middle Aged; D010400:Penicillin G; D010455:Peptides; D011233:Precipitin Tests; D011817:Rabbits; D012882:Skin Tests
D000906:Antibodies; D006241:Haptens; D010455:Peptides; D008239:Lysine; D010400:Penicillin G