Homozygosity in the major histocompatibility complex region influences natural killer cell activity in man

The effect of homozygosity at HLA loci on natural killer (NK) cell activity has been examined. Lymphocytes obtained from heterozygous and homozygous individuals were incubated with 51Cr-labeled, NK-sensitive K562 cells at different effector/target ratios, and lytic activity was determined. Homozygous cells, obtained from individuals who are known HLA homozygotes (homozygous typing cells) and from selected families, had low NK activity compared to those heterozygous donors. This low cytotoxic activity had no correlation with sex, but did correlate with homozygosity at the HLA-A, B and/or DR loci. A significantly lower number of cells, which bind to anti-Leu 7 antibody, was found in homozygous donors. However, this reduced number of Leu 7+ cells could only partially account for the decrease in NK activity. These studies suggest that in some individuals homozygosity at HLA may be linked to genes that control NK activity.