Cellular responses in vitro to H-2D region histocompatibility antigens were demonstrated to be under the genetic control of two or three (P = 0.013) independently segregating loci. The H-2 region itself accounts for one of these loci, however, its activity appears to be dependent upon an association with other non-H-2-associated genetic information. The ability to stimulate a response and to respond to that stimulus are two separate genetic functions in certain MLR combinations. The stimuli in our studies were products of the H-2D region and cell donors must differ at that region in order for a response to occur. The control of the level of responses was determined by other genetic material. Differences at these "response loci" were not necessary for the induction of a proliferative response in the mixed lymphocyte cultures.

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