Author
Listed:
- Sungjin Kim
(Howard Hughes Medical Institute)
- Jennifer Poursine-Laurent
(Howard Hughes Medical Institute)
- Steven M. Truscott
(Pathology and Immunology)
- Lonnie Lybarger
(Pathology and Immunology
University of Arizona)
- Yun-Jeong Song
(Howard Hughes Medical Institute)
- Liping Yang
(Howard Hughes Medical Institute)
- Anthony R. French
(Howard Hughes Medical Institute
Pediatrics)
- John B. Sunwoo
(Howard Hughes Medical Institute
Otolaryngology, Washington University School of Medicine)
- Suzanne Lemieux
(Université du Québec)
- Ted H. Hansen
(Pathology and Immunology)
- Wayne M. Yokoyama
(Howard Hughes Medical Institute
Pathology and Immunology)
Abstract
Self versus non-self discrimination is a central theme in biology from plants1 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 cells2,3,4. 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 genes5,6. 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.
Suggested Citation
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, 2005.
"Licensing of natural killer cells by host major histocompatibility complex class I molecules,"
Nature, Nature, vol. 436(7051), pages 709-713, August.
Handle:
RePEc:nat:nature:v:436:y:2005:i:7051:d:10.1038_nature03847
DOI: 10.1038/nature03847
Download full text from publisher
As the access to this document is restricted, you may want to search for a different version of it.
Citations
Citations are extracted by the
CitEc Project, subscribe to its
RSS feed for this item.
Cited by:
- repec:plo:pone00:0006046 is not listed on IDEAS
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:436:y:2005:i:7051:d:10.1038_nature03847. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
We have no bibliographic references for this item. You can help adding them by using this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.