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Licensing of natural killer cells by host major histocompatibility complex class I molecules
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Journal Article
Licensing of natural killer cells by host major histocompatibility complex class I molecules
2005
Overview
Self versus non-self discrimination is a central theme in biology from plants
1
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
2
,
3
,
4
. 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
5
,
6
. 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.
Publisher
Nature Publishing Group UK,Nature Publishing,Nature Publishing Group
Subject
/ Biological and medical sciences
/ Fundamental and applied biological sciences. Psychology
/ Histocompatibility Antigens Class I - immunology
/ Humanities and Social Sciences
/ Immune Tolerance - immunology
/ Interferon-gamma - biosynthesis
/ Interferon-gamma - immunology
/ Intracellular Signaling Peptides and Proteins
/ Killer Cells, Natural - cytology
/ Killer Cells, Natural - immunology
/ Killer Cells, Natural - metabolism
/ letter
/ Ligands
/ Mice
/ Mutation
/ Protein Tyrosine Phosphatase, Non-Receptor Type 6
/ Protein Tyrosine Phosphatases - metabolism
/ Science
