BINDING OF DIVERSE PEPTIDES TO MHC CLASS-I MOLECULES INHIBITS TARGET-CELL LYSIS BY ACTIVATED NATURAL-KILLER-CELLS

Class I MHC expression by target cells inhibits lysis mediated by natu ral killer (NK) cells, often in an allele-specific fashion. It has bee n proposed that NK cell inhibitory receptors recognize complexes of cl ass I molecules with specific cellular peptides that define self, disp lacement of which would render cells NK sensitive. By loading the most ly empty D-d class I molecules of cell lines deficient in peptide tran sporter molecules with synthetic or natural D-d-bound peptides, we hav e demonstrated specific dose-dependent inhibition of the Ly49(+) subse t of activated NK cells by class I-peptide complexes. Inhibition occur red with most if not all Dd-binding peptides, suggesting that Ly49(+) NK cells recognize class I-peptide complexes largely independently of peptide composition. The results suggest a primary role of NK cells in the destruction of cells that have down-regulated or extinguished cel l surface expression of some or all class I molecules.