Cooperation between Carrier-reactive and Hapten-sensitive Cells <Emphasis Type="Italic">in vitro</Emphasis>

THE mechanism, known as the carrier effect, whereby immunity to one or more determinant groups enhances the response to other determinants on the same multivalent antigen, was first recognized in delayed hypersensitivity to haptens, in which, for an appreciable response, the hapten must be coupled to the same protein carrier for priming and challenge^{1, 2}. Carrier specificity has also been demonstrated in the secondary antibody responses to hapten protein conjugates³. Two alternative hypotheses have been advanced to explain this specificity. The “local environment” hypothesis supposes that the hapten-sensitive cell recognizes both the hapten and the carrier determinants. However, the antihapten antibodies produced do not distinguish details of the carrier molecule and so do not reflect the specificity of the cellular receptor. Furthermore, inert spacer molecules inserted between hapten and carrier do not interfere with carrier specificity in the antibody response³. Reflecting current views on the cooperation between thymus-derived (T) and bone marrow derived (B) lymphocytes in the antibody response to various antigens⁴, the second hypothesis invokes two or more cells, one with receptors directed towards the hapten (hapten-sensitive cell), the others specific for the carrier molecule proper (carrier-reactive cells). Supporting this is the observation that pre-immunization to a particular protein carrier alone could potentiate the primary or secondary antihapten response to a hapten conjugated to that protein⁵. In an adoptive transfer system, moreover, the efficiency of antihapten antibody production by cells primed to a particular hapten-protein conjugate and stimulated with the hapten conjugated on a heterologous protein, is significantly enhanced by the introduction of cells primed to the heterologous carrier alone. Anti-carrier serum antibody does not cause such enhancement⁶. The carrier-reactive cells must therefore cooperate in increasing the efficiency of the hapten-sensitive cells in some way other than by providing humoral anti-carrier antibody. Recent work strongly suggests that carrier reactive cells are thymus-derived^{6, 7}.