The carrier effect in the secondary response to haptenprotein conjugates. Cellular cooperationThe adoptive secondary response of mice t o conjugates of NIP (4-hydroxy-Siodo-3-nitro-phenacetyl-) and DNP (2,4-dinitrophenyl-) is here used to elucidate the mechanism of cellular cooperation. The framework into which the experiments fit can be formulated as follows. Priming immunization raises a crop not only of specific antibody-forming-cell-precursors (AFCP) but also of specific helper cells. Upon secondary stimulation the helper cells serve a role as handlers or concentrators of antigen, thus enabling AFCP which would otherwise be incapable of reacting t o initiate antibody synthesis. In this act of cooperation both cells recognise antigen; in the system examined here the helpers recognise carrier determinants and the AFCP recognise either the hapten or other carrier determinants.The first aim of the experiments was t o raise populations of helpers and AFCI' of distinguishable specificity. Mice were primed with NIP-Ovalbumin (OA) mixed with chicken y-globulin (CGG) and bovine serum albumin (BSA); in comparison with controls primed with unmixed NIP-OA, their cells after transfer were relatively more sensitive t o secondary stimulation with NIP-CGG or NIP-BSA and similar findings were obtained in cross-checks of these carriers. For reasons which are not entirely clear, non-transferred cells did not show the same effect. In further experiments cells primed with one conjugate (e. g. NIP-OA) were mixed with cells primed with another protein (e. g. BSA), transferred and challenged with the hapten conjugated t o the second protein (i. e.NIP-BSA). In comparison with controls lacking the protein-primed cells, the mixture regularly showed greater sensitivity t o stimulation. NIP and DNP were tested in many of the possible combinations with BSA, OA and CGG with the same result. The mixture system was used in the further analysis.Tests with aHotype-marked protein-primed cells showed that these cells did not participate in the production of the anti-hapten antibody and could therefore properly be regarded as helpers. Tests of specificity showed that physical union of the hapten and carrier were required: cells primed with BSA, for example, would not help NIP-OA-primed cells t o make a response t o NIP-HSA even when stimulated at the same time with BSA. Transfer of less than one-tenth of the spleen gives a maximum helper effect, whereas AFCP activity continues t o rise as larger numbers of cells are transferred. Helper cells are therefore normally present in excess.Helper activity is more resistant than AFCP activity t o irradiation, drugs and semi-allogeneic cell transfer across an H-2 barrier. This suggests that helper cells play a relatively passive role in the immune response.Several observations indicate that helper cells are thymus-derived mediators of cellular immunity. Passively transferred antibody did not substitute for helper cells. After immunization helper activity developed faster than AFCP activity. Spleen cells o...

The liver/serum protein F appears to inactivate clones reactive towards itself in the T helper cell but not the B cell compartment. To examine the extent of self-reactivity in the T suppressor cell compartment, the well-established procedure of i.v. injecting milligram doses of the protein was used. To detect suppression, an entirely in vitro proliferation assay was devised, based on use of immunopurified F antigen. In this way T suppressor cells could be detected after activation either by allogeneic F, or (though to a lesser extent) by self-F protein. Thus the T suppressor cell compartment contains potentially self-reactive clones, and to that extent the receptor repertoire of T suppressor cells overlaps with B rather than T helper cells.

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