Genetic and Cellular Aspects of Xenogeneic Mixed Leukocyte Culture Reaction* by Kirsten Fischer Lindahl* and Fritz H. Bach

Xenogeneic lymphocytes can induce proliferative responses in the mixed lymphocyte culture (MLC) ~ which are as strong as those induced by allogeneic lymphocytes (1). It is impossible to determine directly which lymphocyte antigens stimulate the xenogeneic MLC response. The recently described "primed lymphocyte typing" (PLT) assay (2) has made it possible to determine indirectly the genetic control of xenogeneic MLC. Sensitization in a mixed lymphocyte culture positively selects for memory cells which give a rapid secondary response upon restimulation with cells from the initial stimulator (3, 4). Studies in human families (2, 5-7) showed that restimulation is caused by the same LD determinants of the major histocompatibility complex (MHC) that induce primary MLC responses. In this paper we present studies of human lymphocytes which were sensitized to cells of a single mouse strain and restimulated with cells from a variety of strains. By choosing combinations of primary and secondary stimulator which shared only certain parts of their genetic material, we could assay the relative importance of non-H-2 and various H-2 antigens for activation of human lymphocytes. The results suggest that the same antigens are important in allogeneic and xenogeneic MLC reactions. The ability of human leukocyte subpopulations to respond in xenogeneic MLC further suggest that the cellular requirements of allogeneic and xenogeneic MLC responses are the same.