Carrier Function in Anti-Hapten Antibody Responses

Abstract

Guinea pigs primed with 2,4-dinitrophenyl (DNP)-ovalbumin (OVA) will develop markedly enhanced secondary anti-DNP antibody responses to the heterologous conjugate DNP-bovine γ globulin (BGG) provided that they have been supplementally immunized with appropriate amounts of BGG. This phenomenon reflects the enhancing influence of BGG-specific thymus-derived (T) lymphocytes on anti-DNP antibody production. The present studies demonstrate that such enhancing T cell influences can be abolished by the following manipulations: 1) simultaneous supplemental immunization with two unrelated proteins such as BGG and keyhole limpet hemocyanin (KLH) or glucose oxidase (GO) significantly diminished the secondary anti-DNP response upon challenge with a DNP-conjugate of one of the carriers employed; 2) the intraperitoneal injection of soluble BGG, in the appropriate dose range, 1 day before secondary DNP-BGG challenge completely abolishes the anti-DNP response regardless of whether BGG alone or BGG together with KLH had been used in the supplemental immunization; 3) a challenge with soluble KLH 1 day before secondary challenge with DNP-BGG inhibits the anti-DNP response provided KLH had been administered simultaneously with BGG in the supplemental immunization. The failure to observe similar suppression when KLH was replaced by a copolymer of d-glutamic acid and d-lysine (D-GL) which is nonimmunogenic for T cells indicates that this suppression is a reflection of a T cell-mediated influence.

We have interpreted these observations to indicate the production of soluble inhibitory mediators in phenomena such as antigen-induced suppression (“antigenic competition”) and, furthermore, that the elaboration of such mediators is most likely by T lymphocytes. Reasons for favoring the concept that enhancing or inhibitory influences on antibody production represent two ends of the spectrum of regulation exerted, perhaps, by the same T cell product are discussed.