Specificity of murine delayed-type hypersensitivity to conjugates of large or small haptens on protein carriers bearing lipid groups

Abstract

Delayed-type hypersensitivity (DH) in the mouse was provoked with different hapten-carrier complexes mixed with the cationic, surface-active lipid, dimethyl dioctadecyl ammonium bromide (DDA). DH was measured as footpad swelling. Conjugates of bovine serum albumin (BSA) with the small haptens dinitrophenyl (DNP), 'arsonate' (ARS) and 'sulphonate' (SULPH) served to generate strong DH reactions towards the homologous antigen. Insertion of a tripeptide spacer between the hapten and carrier resulted in lower DH reactivity. Optimal dosages and optimal time intervals between sensitization and DH elicitation were determined for the enlarged hapten-carrier complexes. Cyclophosphamide (CY) treatment, before priming with complexes mixed with DDA, caused a 5-6 day delay in the expression of DH but failed to evoke enhanced DH for any of the antigens tested. A broad array of cross reactions between small and enlarged hapten-carrier complexes showed a relative lack of specificity in these DH responses. The results are compared with others reported in the literature and are explained mainly by the effects of electrostatically bound lipid groups of DDA in the sensitizing conjugates.