NK-mediated elimination of mutant lymphocytes that have lost expression of MHC class I molecules

Kusunoki Y, Kyoizumi S, Honma M, Kubo Y, Ohnishi H, Hayashi T, Seyama T
J Immunol 165:3555-63, 2000

Summary

We tested the hypothesis that mutant lymphocytes lacking expression of MHC class I molecules are eliminated by autologous NK cells. In H-2^b/k F1 mice, the frequency of H-2K^b-negative T cells was higher than that of H-2K^k-negative T cells. The frequency of H-2K-deficient T cells increased transiently after total body irradiation. During recovery from irradiation, H-2K^k-negative T cells disappeared more rapidly than H-2K^b-negative T cells. The disappearance of H-2K-deficient T cells was inhibited by administration of antibody against asialo-GM1. H-2K^k-negative T cells showed higher sensitivity to syngeneic NK cells in vitro when compared to H-2K^b/k heterozygous or H-2K^b-negative T cells. Adding syngeneic NK cells to in vitro cultures prevented emergence of mutant cells lacking H-2K^k expression but had little effect on the emergence of mutant cells lacking H-2K^b expression. In H-2^b/d F1 mice, there was no significant difference between the frequencies of H-2K^b-negative and H-2K^d-negative T cells, although the frequencies of mutant cells were different after radiation exposure among the strains examined. H-2^b/d F1 mice also showed rapid disappearance of the mutant T cells after irradiation, and administration of antibody against asialo-GM1 inhibited the disappearance of H-2K-deficient T cells in H-2^b/d F1 mice. Our results provide direct evidence that autologous NK cells eliminate mutant cell populations that have lost expression of self-MHC class I molecules.