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J Exp Med. 2014 Nov 17;211(12):2455-65. doi: 10.1084/jem.20140798. Epub 2014 Nov 3.

Antigen-specific expansion and differentiation of natural killer cells by alloantigen stimulation.

Author information

1
Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143 Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143 Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki 305-8577, Japan.
2
Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143 Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143 Lewis.Lanier@ucsf.edu.

Abstract

Natural killer (NK) cells provide important host defense against microbial pathogens and can generate a population of long-lived memory NK cells after infection or immunization. Here, we addressed whether NK cells can expand and differentiate after alloantigen stimulation, which may be important in hematopoietic stem cell and solid tissue transplantation. A subset of NK cell in C57BL/6 mice expresses the activating Ly49D receptor that is specific for H-2D(d). These Ly49D(+) NK cells can preferentially expand and differentiate when challenged with allogeneic H-2D(d) cells in the context of an inflammatory environment. H-2D(d) is also recognized by the inhibitory Ly49A receptor, which, when coexpressed on Ly49D(+) NK cells, suppresses the expansion of Ly49D(+) NK cells. Specificity of the secondary response of alloantigen-primed NK cells was defined by the expression of activating Ly49 receptors and regulated by the inhibitory receptors for MHC class I. Thus, the summation of signals through a repertoire of Ly49 receptors controls the adaptive immune features of NK cells responding to allogeneic cells.

PMID:
25366966
PMCID:
PMC4235640
DOI:
10.1084/jem.20140798
[Indexed for MEDLINE]
Free PMC Article

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