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

Sung Jin 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 journalArticle

850 Citations (Scopus)

Abstract

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
JournalNature
Volume436
Issue number7051
DOIs
StatePublished - Aug 4 2005
Externally publishedYes

Fingerprint

Licensure
Major Histocompatibility Complex
Natural Killer Cells
Self Tolerance
Vertebrates
Lymphocytes
Cytoplasmic and Nuclear Receptors
Immunotherapy
Mental Competency
Genes
Immune System
Cytokines
Population

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Kim, S. J., Poursine-Laurent, J., Truscott, S. M., Lybarger, L., Song, Y. J., Yang, L., ... Yokoyama, W. M. (2005). Licensing of natural killer cells by host major histocompatibility complex class I molecules. Nature, 436(7051), 709-713. https://doi.org/10.1038/nature03847

Licensing of natural killer cells by host major histocompatibility complex class I molecules. / Kim, Sung Jin; Poursine-Laurent, Jennifer; Truscott, Steven M.; Lybarger, Lonnie; Song, Yun Jeong; Yang, Liping; French, Anthony R.; Sunwoo, John B.; Lemieux, Suzanne; Hansen, Ted H.; Yokoyama, Wayne M.

In: Nature, Vol. 436, No. 7051, 04.08.2005, p. 709-713.

Research output: Contribution to journalArticle

Kim, SJ, Poursine-Laurent, J, Truscott, SM, Lybarger, L, Song, YJ, Yang, L, French, AR, Sunwoo, JB, Lemieux, S, Hansen, TH & Yokoyama, WM 2005, 'Licensing of natural killer cells by host major histocompatibility complex class I molecules', Nature, vol. 436, no. 7051, pp. 709-713. https://doi.org/10.1038/nature03847
Kim SJ, Poursine-Laurent J, Truscott SM, Lybarger L, Song YJ, Yang L et al. Licensing of natural killer cells by host major histocompatibility complex class I molecules. Nature. 2005 Aug 4;436(7051):709-713. https://doi.org/10.1038/nature03847
Kim, Sung Jin ; Poursine-Laurent, Jennifer ; Truscott, Steven M. ; Lybarger, Lonnie ; Song, Yun Jeong ; Yang, Liping ; French, Anthony R. ; Sunwoo, John B. ; Lemieux, Suzanne ; Hansen, Ted H. ; Yokoyama, Wayne M. / Licensing of natural killer cells by host major histocompatibility complex class I molecules. In: Nature. 2005 ; Vol. 436, No. 7051. pp. 709-713.
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