Licensing of natural killer cells by host major histocompatibility complex class I molecules

Sungjin Kim, Jennifer Poursine-Laurent, Steven M. Truscott, Lonnie Lybarger, Yun Jeong Song, Liping Yang, Anthony R. French, John B. Sunwoo, Suzanne Lemieux, Ted H. Hansen, Wayne M. Yokoyama

Research output: Contribution to journalArticlepeer-review

1063 Scopus citations


Self versus non-self discrimination is a central theme in biology from plants to vertebrates, and is particularly relevant for lymphocytes that express receptors capable of recognizing self-tissues and foreign invaders. Comprising the third largest lymphocyte population, natural killer (NK) cells recognize and kill cellular targets and produce pro-inflammatory cytokines. These potentially self-destructive effector functions can be controlled by inhibitory receptors for the polymorphic major histocompatibility complex (MHC) class I molecules that are ubiquitously expressed on target cells. However, inhibitory receptors are not uniformly expressed on NK cells, and are germline-encoded by a set of polymorphic genes that segregate independently from MHC genes. Therefore, how NK-cell self-tolerance arises in vivo is poorly understood. Here we demonstrate that NK cells acquire functional competence through 'licensing' by self-MHC molecules. Licensing involves a positive role for MHC-specific inhibitory receptors and requires the cytoplasmic inhibitory motif originally identified in effector responses. This process results in two types of self-tolerant NK cells-licensed or unlicensed-and may provide new insights for exploiting NK cells in immunotherapy. This self-tolerance mechanism may be more broadly applicable within the vertebrate immune system because related germline-encoded inhibitory receptors are widely expressed on other immune cells.

Original languageEnglish (US)
Pages (from-to)709-713
Number of pages5
Issue number7051
StatePublished - Aug 4 2005

ASJC Scopus subject areas

  • General


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