Natural killer cell crossmatch: Functional analysis of inhibitory killer immunoglobulin-like receptors and their HLA ligands

Attempts to predict outcome of bone marrow transplantation based on killer immunoglobulin-like receptor (KIR) and HLA genotyping have yielded discordant results. To better understand the factors involved, we investigated natural killer (NK) cell function and correlated it with genetics and expression of inhibitory KIR and HLA ligands in 20 normal allogeneic pairs. KIR expression was analyzed by flow cytometry to estimate the percentage of NK cells that could be inhibited by the HLA ligands in each pair combination. NK cytotoxicity against ConA blasts demonstrated a positive correlation between the number of KIR/HLA matches and the predicted number of NK cells that could be inhibited. When 50% or more of the NK cells could be inhibited, cytotoxicity was lower (8%) than when 25% or less of the NK cells expressed KIR with matched HLA (49%) (p < 0.0001). Our data suggest that the interaction between inhibitory KIR and HLA ligands can be correlated to some extent with NK cell function, but measurement of NK activity may provide the best information for analysis of clinical situations.