Building tolerance by dismantling synapses: inhibitory receptor signaling in natural killer cells


Correspondence to:

Morgan Huse

Immunology Program, Memorial Sloan-Kettering Cancer Center

1275 York Ave., Box 514

New York, NY 10065, USA

Tel.: +1 646 888 2379

Fax: +1 646 422 0502



Cell surface receptors bearing immunotyrosine-based inhibitory motifs (ITIMs) maintain natural killer (NK) cell tolerance to normal host tissues. These receptors are difficult to analyze mechanistically because they block activating responses in a rapid and comprehensive manner. The advent of high-resolution single cell imaging techniques has enabled investigators to explore the cell biological basis of the inhibitory response. Recent studies using these approaches indicate that ITIM-containing receptors function at least in part by structurally undermining the immunological synapse between the NK cell and its target. In this review, we discuss these new advances and how they might relate to what is known about the biochemistry of inhibitory signaling in NK cells and other cell types.