Carrier Function in Anti-Hapten Immune Responses

Abstract

The introduction of defned haptenic determinants into immunogenic carriers by Landsteiner (1) has provided a poweriul tool for the analysis of specific interactions between antigens and specific ceils in the immune response. Considerable evidence has been obtained demonstrating that cellular immune reactions to hapten-protein conjugates (delayed sensitivity [2-@ stimulation of DNA synthesis by antigen [7,8], and hapten-specific secondary responses [9-111) display a significant although variable degree of carrier specificity. Such carrier specificity of hapten-specific cellular reactions was initially interpreted to reflect the partial specificity of the antigen-binding receptors of specific cells for the carrier molecule (12-16), paralleling the demonstrated carrier specificity of anfi-hapten humoral antibodies (16)(17)(18).This interpretation of carrier function, however, is not able to explain several essential characteristics of hapten-specific immune responses:(a) The magnitude of the carrier specificity of cellular immune reactions cannot be easily explained by the relatively modest contribution, in energetic terms, of the carrier molecule to the specificity of most anti-hapten humoral antibodies (16-18):(b) Hapten conjugates of immunogenic molecules are required to elicit strong antihapten antibody responses; nonimmunogenic substances serve only poorly, or not at all, as carriers for haptens (19)(20)(21).(e) The induction of immunological unresponsiveness to the carrier molecule results in the partial or total suppression of the responses to haptens on the tolerated proteins (22)(23)(24)(25)(26)(27).If the specificity of serum antibody accurately expresses the specificity of the antigenbinding receptors present on the precursors of antibody forming cells, then these findings suggest the operation o[ an additional recognition mechanism for the carrier molecule. This interpretation would be strengthened if cooperation between carrier-specific and hapten-specific cells were found to be essential for the development of anti-hapten immune responses. According to this view, cells capable o[ reacting with carrier molecules should interact with the antigen be[ore anti-hapten antibody producing cells could be stimulated by hapten-protein conjugates.Mitchison (28) and Rajewsky et al. (29), have recently demonstrated such cooperation between carrier-specific cells and hapten-specific cells in anti-hapten secondary 261

Hapten-Specific Tolerance

“…affinity of serum anti-DNP antibody for ~-DNP-L-lysine was evaluated by the comparison of antigen-binding capacity in a Farr assay (18) at a standard concentration of bound and free ligand with that at several other concentrations of bound and free ligand, e-DNP-L-lysine-aH (14-25 Ci/mM), prepared as previously described (12,19), at a final concentration of either 0.5 X 10 -a, 0.5 N 10 -7, or 0.5 X 10 -8 M, was mixed with antiserum or antiserum diluted in 10% normal guinea pig serum. After 30 rain, an equal volume of saturated ammonium sulfate was added; 30 rain later the suspension was centrifuged at 2500 rpm at 4°C, and a measured aliquot of supernatant added to 6 ml of Aquasol (New England Nuclear Corp.).…”

Immunodeviation by Passive Antibody, an Expression of Selective Immunodepression

“…Indeed, the use of complete Freund's adjuvant for sensitization in the studies on the carrier effect induces DH to the carrier (13,16,17). Carrier and hapten determinants are unrelated, separate determinants (14, 17); this conclusion is strongly favored by experiments where tolerance to the carrier reduces the response to the hapten (13,18,19).…”

“…On the other hand, a cooperating role of anticarrier antibody appears to be invalidated by several experiments (16,17,29). When given passively, anticarrier antibodies either have no effect (6,29) or yield a considerable depression of the antihapten response (16,30).…”

“…When given passively, anticarrier antibodies either have no effect (6,29) or yield a considerable depression of the antihapten response (16,30).…”

Dual Regulatory Role of the Thymus in the Maturation of Immune Response in the Rabbit

“…Katz et al (10) reported that the primary antihapten antibody response of rabbits and guinea pigs to a hapten coupled to a carrier was enhanced if the animals had been preimmunized with small doses of free carrier. Carrier preimmunization had no effect on the affinity of the antihapten antibody, however.…”