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Culture conditions have been established that allow the induction of delayed-type hypersensitivity (DTH) precursor cells present in a cell population derived from unsensitized spleen cells only when antigen-specific, radioresistant, Thy-1-bearing helper cells are added. This specific cellular cooperation acts via the linked recognition of two determinants on the antigen; thus, cells primed to the protein antigen fowl gamma globulin (FGG) will only allow the induction of DTH reactivity against the second antigen, burro erythrocyte (BRBC), when the conjugate FGG-BRBC is present in the cultures. The requirement for physical linkage between the two antigens has been demonstrated by the observation that DTH to BRBC is induced when the conjugate FGG-BRBC is present and not when BRBC and FGG are given an uncoupled molecules.

T cells cooperating in the induction of delayed-type hypersensitivity act via the linked recognition of antigenic determinants.