ANALYSIS OF THE ANTIGENIC RELATIONSHIP OF VARIOUS DERIVATIVES OF N-ACETYL-MURAMYL-L-ALA-D-ISOGLUTAMINE (MDP), USING ANTI-MDP ANTIBODIES

Antibodies to N-acetyl-muramyl-L-alanyl-D-isoglutamine (muramyl dipeptide, MDP) were produced in rabbits by injection of MDP conjugated to various carriers [bovine .gamma.-globulin (BGG), methylated bovine serum albumin or sheep erythrocytes]. The anti-MDP was assayed by a direct enzyme-linked immunosorbent assay (ELISA) using horseradish peroxidase linked to MDP-Lys. Various derivatives of MDP were employed in an inhibition of ELISA for analysis of specificity of antibodies and study of the relationship of configuration to biological activity. MDP alone apparently is not immunogenic but can act as a hapten when conjugated to carriers. The antibodies were primarily directed against the muramyl residue. Modifications of this region of MDP yielded derivatives with weak reactivity against anti-MDP, while some changes of other regions had no effect on its antigenicity. Optical isomers of MDP had reduced activity as compared to MDP and polymeric MDP was a strong inhibitor. The structure and function relationship is discussed for some derivatives.