Immunochemical Studies on Delayed and Arthus-Type Hypersensitivity Reactions

Summary Studies of the immunochemical relationships between delayed and Arthus-type hypersensitivity reactions in guinea pigs sensitized to α, DNP, oligo-l-lysyl peptides have led to several observations. 1) Small nonimmunogenic members of the homologous series of peptides elicit only Arthus-type reactions. 2) Larger members which are immunogenic provoke both Arthus and delayed reactions. 3) Serum antibodies from these animals have permitted studies of quantitative inhibition of precipitation; the peptides show increasing efficiency of inhibition, on a molar basis, with increasing chain length, up to the heptamer. 4) The upper limit of combining-site size in this system appears complementary to the heptamer. 5) The maximum combining-site size corresponds in size to the smallest peptide in this series which is immunogenic. 6) Although the hexamer contributes approximately 96% of the binding energy of the heptamer with conventional antibody, the heptamer, but not the hexamer, elicits a delayed reaction. These results suggest that circulating high affinity antibody or antibody with a larger combining site is not the mediator of the delayed response. Since only immunogenic peptides provoke the delayed skin reaction in this system, the delayed response may depend on local biosynthesis of sufficient antibody (cell-bound or free) by sensitized lymphocytes to form antigen-antibody complexes capable of producing tissue damage. Under these circumstances, the need for a larger determinant to elicit the delayed response reflects on the immunogenicity of the material and not its complementariness to a combining site size on a preformed antibody molecule.