A dual receptor system composed of activation and inhibitory receptors apparently controls NK cell-mediated lysis. In the C57BL/6 mouse, the NK1.1 molecule acts as an activation receptor whereas Ly-49A, C and G2 can inhibit NK cell lysis of target cells expressing specific MHC class I molecules. We previously reported that NK2.1 is an activation receptor sharing structural properties with members of the NKR-P1 and Ly-49 receptor families. In this study, we have shown that NK2.1 is encoded by the previously described Ly-49C gene. We also found that the expression level of NK2.1/Ly-49C is modulated by H-2-dependent factors and that this regulation differs from that previously described for Ly-49A. Flow cytometry analyses of NK-enriched spleen cells from MHC congenic strains on C57BL/10 and BALB/c backgrounds indeed revealed that the level of NK2.1/Ly-49C expression, but not the number of positive cells, is low in strains expressing H-2b and H-2k haplotypes as compared to H-2d mice. Similar analyses of splenic NK cells from two series of congenic and congenic recombinant strains on the C57BL/10 background indicate that the main regulatory element(s) are most likely the H-2Kb and H-2Dk alleles. Together with our and others previous observations, these results identify the NK2.1/Ly-49C antigen as a receptor for MHC class I molecules whose expression is regulated by host MHC genes.

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SUMMARYSpleen cells hat^ested from tnice infected intraperitoneally with M. lepraemurium 11 17 weeks prior to harvest acquired the capacity lo inhibit concanavalin A (Con A) induced proliferation of normal spleen cells when precullured for up to 24 h in mitogen-frec medium. The in vitro induced suppressor activity correlated with the length of the prccullure period, the time post-infection and ihc infecting dose. These lindings were interpreted as an indication thai suppressor cell precursors aeeumulated in the spleen of infected mice during the early phase of the disease. The interaction of infectiondependent adherent suppressor eell preeursors and infection-independent, non-adherent regulatory cells is necessary lor the suppressor activity to develop. Both the cells which transmit the inductive signal and the precursor eells which mature into active suppressor eells are radiosensitive, whereas suppressor activity itself is a funetion of radioresistanl adherent cells. Preculture of cells for a short period.before they were coeuttured with Con A-stimulaied normal spleencells. allowed the deteetion of suppressor cells hefore they were deleterious to the infected hosl and also turned out to be a relevatit //; vitro model for characterization of suppressor cell development during M. lepractmirium infection.

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