Functionally and Structurally Distinct NK Cell Receptor Repertoires in the Peripheral Blood of Two Human Donors

TLDR

The study profiled KIR and CD94:NKG2 receptor expression on over 100 NK cell clones from two donors with distinct HLA‑KIR genotypes. More than 98 % of clones were inhibited by autologous class I allotypes, and inhibition patterns matched receptor specificity, with donor 1, having three KIR ligands, predominantly using KIR and capable of killing donor 2’s cells, while donor 2, with only one KIR ligand, relied on CD94:NKG2a and tolerated donor 1’s cells.

Abstract

The expression of KIR and CD94:NKG2 receptors was determined for more than 100 natural killer (NK) cell clones obtained from two blood donors who differ in their HLA class I and KIR genes. More than 98% of the clones were inhibited by individual autologous class I allotypes, and every clone was inhibited by the combination of autologous allotypes. The patterns of inhibition correlate with expression of inhibitory receptors of defined specificity. One donor possesses three class I ligands for KIR, and a majority of NK cells use KIR as their inhibitory receptor; the second donor possesses only a single ligand for KIR, and a majority of NK cells use the more broadly reactive CD94:NKG2a as their inhibitory receptor. Because of these differences, the first donor has subpopulations of NK cells that kill cells of the second donor, whereas the NK cells of the second donor are universally tolerant of cells from the first donor.