Structural basis for immune recognition of lysozymes. II. Reactive but non‐immunogenic epitopes

Certain epitopes on protein molecules are reactive with antibody but are not immunogenic. Rabbit antiserum prepared against hen egg‐white lysozyme (HEL) reacted poorly or not at all with peptides LH II (a. a. 13‐105) and LH III (a. a. 106‐129) derived from the action of CNBr on reduced HEL (HEL (CB)). In sharp contrast, antiserum raised (a) to the derivative HEL (CB) with two peptide chain cleavages at methionines 12 and 105, or (b) to bob‐white lysozyme (BEL), reacted with peptides LH II and LH III . These peptides were able to compete directly with HEL in a 125 I‐HEL‐anti‐HEL(CB) system, or an 125 I‐HEL‐anti‐BEL system, but could not inhibit the 125 I‐HEL‐anti‐HEL reaction. The results demonstrate that some epitopes on HEL(CB) or BEL are reactive and immunogenic, while the same or related epitopes on HEL, although reactive with antibodies directed against them, are not immunogenic. Such epitopes are referred to as hetero topes (epitopes definable by their reactivity on a related, hetero logous protein). The usage of a chemical derivative of HEL allowed the localization of another heterotope region close to tryptophan 62. The existence of heterotopes was discussed in terms of current models of cellular cooperation. The view was advaced that the activation of a particular antibody‐producing precursor cell is dependent on a special steric relationship of carrier to haptenic epitopes.