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

Mutant cells generated in vivo can be eliminated when mutated gene products are presented as altered MHC/peptide complexes and recognized by T cells. Diminished expression of MHC/peptide complexes enables mutant cells to esca pe recognition by T cells. In the present study, we tested the hypothesis t hat mutant lymphocytes lacking expression of MHC class I molecules are elim inated by autologous NK cells. In H-2(b/k) F-1 mice, the frequency of H-2K( b)-negative T cells was higher than that of H-2K(k)-negative T cells. The f requency of H-2K-deficient T cells increased transiently after total body i rradiation. During recovery from irradiation, H-2K(k)-negative T cells disa ppeared more rapidly than H-2K(b)-negative T cells. The disappearance of H- 2K-deficient T cells was inhibited by administration of Ab against asialo-G M1. H-2K(k)-negative T cells showed higher sensitivity to autologous NK cel ls in vitro than H-2K(b/k) heterozygous Or H-2K(b)-negative T cells. Adding syngeneic NK cells to in vitro cultures prevented emergence of mutant cell s lacking H-2K(k) expression but had little effect on the emergence of muta nt cells lacking H-2K(b) expression. Results in the H-2(b/k) F-1 strain cor respond with the sensitivity of parental H-2-homozygous cells in models of marrow graft rejection. In H-2(b/d) F-1 mice, there was no significant diff erence between the frequencies of H-2K(b)-negative and H-2K(d)-negative T c ells, although the frequencies of mutant cells were different after radiati on exposure among the strains examined, H-2(b/d) F-1 mice also showed rapid disappearance of the mutant T cells after irradiation, and administration of Ab against asialo-GM1 inhibited the disappearance of H2K-deficient T cel ls in H-2(b/d) F-1 mice. Our results provide direct evidence that autologou s NK cells eliminate mutant cell populations that have lost expression of s elf-MHC class I molecules.