Differential expression of inhibitory and activating CD94/NKG2 receptors on NK cell clones

Natural killer cells are known to express a variety of surface receptors involved in HLA class I monitoring. It is thus of interest to investigate the clonal distribution and relative expression levels of activating versus inhibitory NK receptors. We have developed a quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) assay designed to determine specific and absolute mRNA levels for NKG2-A/B, -C, -E, -F, -H and NKG2-D. When analyzing NK cell clones derived from a single donor we found differential expression of inhibitory (NKG2-A/B) versus triggering (NKG2-C and potentially -E, -F, -H) NK receptor chains. The generation of the splice variants NKG2-E and -H seemed to occur at a constant ratio. We further compared NKG2 transcript levels to surface receptor expression as monitored by flow cytometric analysis and to NK cell cytotoxicity as detected by reverse ADCC: a clear correlation was observed. Thus, the data obtained reveal a substantial variability in the NKG2 repertoire among NK cell subpopulations, which is likely to affect the sensitivity and reactivity towards the ligand HLA-E.