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The low affinity 40,000 Fc gamma receptor and the transferrin receptor can be alternative or simultaneous target structures on cells sensitive for natural killing






Journal of Immunology 136(12): 4714-4720

The low affinity 40,000 Fc gamma receptor and the transferrin receptor can be alternative or simultaneous target structures on cells sensitive for natural killing

The role of the low avidity 40,000 dalton receptor for IgG (Fc.gamma.R) present on K562 and U937 cells in sensitivity to natural killing (NK) was studied by using a murine monoclonal antibody (mAb) specific for the 40,000 dalton Fc.gamma.R (.alpha.Fc.gamma.R mAb). Pretreatment of K562 target cells with intact .alpha.Fc.gamma.R mAb or its Fab fragment or anti-transferrin receptor (.alpha.TFR) mAb partially blocked in a dose-dependent manner, NK activity to K562 cells. However, combined pretreatment with .alpha.Fc.gamma.R and .alpha.TFR mAb completely blocked NK activity against K562 targets. As compared with K562 cells, lower levels of NK were elicited against Molt-4, U937, HL-60, and Daudi targets. Although NK activity to Molt-4 targets was not affected by .alpha.Fc.gamma.R mAb, it was fully prevented by pretreatment with .alpha.TFR mAb. In contrast, NK to U937 cells was not influenced by .alpha.TFR mAb, but it was strongly inhibited by .alpha.Fc.gamma.R mAb. The resistance of 3H-TdR-prelabeled adherent HEp-2 cells to natural cell-mediated cytotoxicity was not affected by either mAb. Lectin-dependent cell-mediated cytotoxicity (LDCC) against HEp-2 cells due to the presence of concanavalin A, and was completely abrogated by pretreatment of the targets with .alpha.TFR mAb, but was unaffected by .alpha.Fc.gamma.R mAb. By use of the flow cytometer, a significant correlation was detected between the relative expression of 40,000 dalton Fc.gamma.R and the susceptibility to NK, whereas the expression of TFR was discordant from NK sensitivity. As determined in the single cell cytotoxicity assay .alpha.Fc.gamma.R mAb reduced the frequency of target binding effector cells without affecting the number of dead bound targets. This pattern of inhibition was found against both K562 and U937 targets. Alternatively, .alpha.TFR mAb inhibited both binding and killing of K562 and Molt-4 targets. Because pretreatment of HEp-2 cells with .alpha.TFR mAb did not influence conjugate formation, the blocking of LDCC to HEp-2 cells by .alpha.TFR mAb can be related to post-binding events. These data show that although both the 40,000 dalton Fc.gamma.R and the TFR can be target structures for NK cell recognition, the TFR may also play an important role in the post-binding events.

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Accession: 006712199

PMID: 3011902



Related references

The low affinity 40 kilodalton fc gamma r and the transferrin receptor can be alternative or simultaneous target structures on cells sensitive for natural killing. Federation Proceedings 45(3): 384, 1986

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