Killer cell inhibitory receptor interactions with HLA class I molecules: implications for alloreactivity and...

Human killer cell inhibitory receptors (KIR) are novel members of the immunoglobulin superfamily of cell surface glycoproteins, which are expressed by lymphocytes with natural killers (NK) and cytotoxic T-cell (CTL) phenotypes. These receptors have specificity for relatively conserved epitopes of HLA-A, -B, and -C class I antigens. Recent studies have identified KIR as being involved in the transmission of negative, inhibitory signaling events to the cytotoxic cell which prevent or diminish target cell lysis. KIR are thus likely to play an important role in the responses of alloreactive NK cells and CTL to allogeneic HLA antigens. In this article, we review the known structural and functional characteristics of KIR, suggest a possible mechanism for the transmission of intracellular negative signaling by these receptors, and discuss the relevance of KIR function and HLA specificity to the clinical transplantation of allogeneic tissues.