Genetic regulation of delayed-type hypersensitivity responses to poly(LTyr,LGu)-poly(DLAla)--poly(LLys). I. Expression of the genetic defect at two phases of the immune process.

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Abstract
Delayed-type hypersensitivity (DTH) responses served as an experimental model for analysis of genetic regulations of T [thymus-derived] cell responses. Educated irradiated cells from H-2b mice mediated responses in syngeneic recipients, whereas mice of the a, d, f, k and s haplotypes were nonresponders to poly(LTyr,LGlu)-poly(DLAla).sbd.poly(LLys) [(T,G)-A.sbd.L]. Cell-mediated immune responsiveness to (T,G)-A.sbd.L is apparently linked to the H-2 complex, as shown for humoral responses. Educated irradiated T cells of F1 hybrids between high and low responders mediated DTH responses, which indicates that the gene(s) controlling the DTH responses is dominant. To analyze the genetic defect in DTH responses to (T,G)-A.sbd.L, the T cell activation phase was separated from the effector phase that was determined in recipient mice. Two nonresponder types were observed. When lymphocytes of the a or k haplotypes were educated in a syngeneic environment and then transferred into hybrids between the parental (nonresponder .times. responder)F1 recipients, DTH responses could have been manifested. No DTH responses could be mediated by transferring educated cells of the H-2s or H-2f origin into the appropriate F1 recipients. Irradiated F1 cells that had been activated to (T,G)-A.sbd.L could not mediate DTH responses in both types of nonresponder recipients. T cells of H-2k or H-2a mice apparently can be activated to generate DTH responses to (T,G)-A.sbd.L and the defect in these mouse strains is apparently expressed in another cell population needed for the manifestation of the DTH reaction in the recipient mice. T cells of H-2s and H-2f origin cannot be activated to (T,G)-A.sbd.L and fail to manifest DTH responses.