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objections to the local environment hypothesisA carrier effect is obtained typically when a hapten-protein conjugate is injected into an animal which has previously been primed with the same hapten conjugated to another carrier protein. Under these circumstances the antihapten secondary response is usually less than that which would have been obtained had the animal been injected with a conjugate prepared with the same carrier as that originally used for priming. Attempts have been made to account for the phenomenon in terms of the local environment hypothesis, which assumes that the receptor on immunologically competent cells recognises the hapten jointly with the area on the complete antigen which surrounds it. Alternatively the phenomenon can be accounted for by the hypothesis of cooperation, which assumes that the antigen is recognised by two receptors, one directed to the hapten and the other to a determinant on the carrier protein.Methods are described which enable carrier effects to be studied quantitatively

Transplantation immunity is the state of heightened resistance to a tissue graft which develops after an earlier graft has been broken down. Techniques for the detection of transplantation immunity have been developed by Medawar (1, 2) for skin, and by Mitchison (3, 4) for transplantable tumors. Ceils from the lymphoid tissue of immunized mice have been shown to possess the power of transferring immunity, by Brncic, Hoecker, and Gasic (5) and Mitchison (3, 4) with transplantable tumors, and by Biningham, Brent, and Medawar (6) with skin homografts. Evidence has been presented by Billingham, Brent, and Medawar that the immunologically activated tissue of the donor continues to function in the host after transfer; for immunity acquired in this way they have coined the term "adoptive immunity."The present experiments were carried out with the intention of establishing the quantitative conditions of transfer of transplantation immunity to tumors; and then to investigate the role of the transferred cells in conferring immunity on their hosts. They have been designed to eliminate antigen transferred with the cells, and also preformed antibody, as playing any significant role in the acquired immunity. They also bear on the problem of whether the transferred cells continue to function in their hosts, or whether the cells of the host are activated.The experimental materials have been confined to transplantable tumors in the mouse. Transplantation immunity and its conditions of transfer are similar for tumors and for normal tissue, and hence the conclusions are likely to be

Using an established i.p. adoptive transfer system in which primed precursors of cytolytic (Tc) cells are combined with primed helper (Th) cells and alloantigen, the three-cell-type hypothesis of T-T cooperation has been tested. This hypothesis assumes that cooperation takes place through the formation of clusters, consisting of one or more Tc precursors plus one or more Th cells binding to antigen on the surface of antigen-presenting cells (APC). By using antigens in which the H-2Db epitopes recognized by the Tc precursors are presented either on the same cell as the BALB minor histocompatibility epitopes recognized by the Th cells, or a different one, the value of epitope-linkage has been explored. Epitope-linkage is found to enhance the response at low concentrations of antigen but not at high ones, in accordance with the prediction that at low concentrations individual APC will usually take up either one antigen or the other but not both from an unlinked mixture, while at high concentrations most APC will take up both whether they are linked or not. In a further test of this hypothesis, no requirement for a cognate T-T interaction could be detected. With the three-cell-type interaction thus better established, its implications in terms of efficiency compared with linked-cognate interactions and its evolution are discussed.

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