Distinct Transcriptional Control Mechanisms of Killer Immunoglobulin-like Receptors in Natural Killer (NK) and in T Cells*

Killer immunoglobulin-like receptors (KIR) are expressed by natural killer (NK) cells and by subsets of CD4+ and CD8+ T cells, which are therefore thought to be subject to similar regulatory mechanisms. Here, we show that the transcriptional machinery to express KIR is limited to NK and T cells; however, the KIR transcriptional control differs between these two types of lymphocytes. T cells selectively express transcriptional activators binding to positions -52 to -61 of the KIR promoter, whereas an AML site around position-98 is relevant for transcription in NK cells. Although KIR expression is restricted to subsets of memory T cells, our studies demonstrate that transcriptional activators for KIRs are not acquired during T cell differentiation but are already present in naïve T cells, suggesting a basic role of KIRs in T cell biology. We suggest that the regulated expression of KIRs in T cells profoundly influences peripheral tolerance and antigen-specific immune responses.