Adjuvant Action of Capsular Polysaccharide of Klebsiella Pneumoniae on Antibody response VI. Site of its Action

Abstract

Using the hapten-carrier system in which the dinitrophenyl group (DNP) served as a B-cell reactive hapten and bovine serum albumin (BSA) or human gammaglobulin (HGG) as a T-cell reactive carrier, we investigated the site of the adjuvant action of the capsular polysaccharide of Klebsiella pneumoniae (CPS-K). CPS-K adjuvant was indispensable in induction of both the primary anti-DNP antibody response and the primary increase in DNP-specific memory by injection of DNP-BSA or DNP-HGG. However, in mice primed with a mixture of BSA and CPS-K, the antibody response and increase in memory were induced by DNP-BSA without the help of CPS-K adjuvant, but not by DNP-HGG. It is likely therefore that the DNP-specific cell function is triggered either by synergistic actions of DNP-BSA or DNP-HGG and CPS-K adjuvant or by those of antigen and the carrier-specific cell function which had been triggered by synergistic actions of carrier and CPS-K adjuvant. The carrier-specific tolerance to DNP-BSA was induced when a large dose of BSA was injected without CPS-K adjuvant, while simultaneous administration of CPS-K adjuvant prevented the induction of tolerance. A secondary injection of DNP-BSA alone into mice primed with a mixture of DNP-BSA and CPS-K adjuvant induced definitely both the secondary anti-DNP antibody response and the secondary increase in DNP-specific memory. CPS-K adjuvant showed only a slight additional effect on them. A secondary injection of DNP-HGG in place of DNP-BSA exhibited no effect in these mice. It is likely therefore that DNP-specific memory is triggered to induce both the secondary anti-DNP antibody response and the secondary increase in DNP-specific memory through the synergistic actions of antigen and the carrier-specific memory which had also been triggered by synergistic actions of carrier and CPS-K. In addition, we also demonstrated that CPS-K adjuvant exhibited a definite mitogenic effect on B cells but not on T cells. From the present experiments it has been concluded that CPS-K adjuvant acts preferentially in triggering virgin T cells and this is the primary site of the adjuvant action of CPS-K, despite the fact that CPS-K does not stimulate the DNA synthesis of T cells polyclonally. It is suggested that the second external signal provided by CPS-K adjuvant is essential for T cells to recognize as nonself the first signal provided by antigen at the initial stage of the immune response.