TY - JOUR
T1 - MHC class I-deficient natural killer cells acquire a licensed phenotype after transfer into an MHC class I-sufficient environment
AU - Elliott, Julie M.
AU - Wahle, Joseph A.
AU - Yokoyama, Wayne M.
PY - 2010/9/27
Y1 - 2010/9/27
N2 - In MHC class I-deficient hosts, natural killer (NK) cells are hyporesponsive to cross-linking of activation receptors. Functional competence requires engagement of a self-major histocompatability complex (MHC) class I-specific inhibitory receptor, a process referred to as "licensing." We previously suggested that licensing is developmentally determined in the bone marrow. In this study, we find that unlicensed mature MHC class I-deficient splenic NK cells show gain-of-function and acquire a licensed phenotype after adoptive transfer into wild-type (WT) hosts. Transferred NK cells produce WT levels of interferon-γ after engagement of multiple activation receptors, and degranulate at levels equivalent to WT NK cells upon coincubation with target cells. Only NK cells expressing an inhibitory Ly49 receptor specific for a cognate host MHC class I molecule show this gain-of-function. Therefore, these findings, which may be relevant to clinical bone marrow transplantation, suggest that neither exposure to MHC class I ligands during NK development in the BM nor endogenous MHC class I expression by NK cells themselves is absolutely required for licensing.
AB - In MHC class I-deficient hosts, natural killer (NK) cells are hyporesponsive to cross-linking of activation receptors. Functional competence requires engagement of a self-major histocompatability complex (MHC) class I-specific inhibitory receptor, a process referred to as "licensing." We previously suggested that licensing is developmentally determined in the bone marrow. In this study, we find that unlicensed mature MHC class I-deficient splenic NK cells show gain-of-function and acquire a licensed phenotype after adoptive transfer into wild-type (WT) hosts. Transferred NK cells produce WT levels of interferon-γ after engagement of multiple activation receptors, and degranulate at levels equivalent to WT NK cells upon coincubation with target cells. Only NK cells expressing an inhibitory Ly49 receptor specific for a cognate host MHC class I molecule show this gain-of-function. Therefore, these findings, which may be relevant to clinical bone marrow transplantation, suggest that neither exposure to MHC class I ligands during NK development in the BM nor endogenous MHC class I expression by NK cells themselves is absolutely required for licensing.
UR - http://www.scopus.com/inward/record.url?scp=77957724586&partnerID=8YFLogxK
U2 - 10.1084/jem.20100986
DO - 10.1084/jem.20100986
M3 - Article
C2 - 20819924
AN - SCOPUS:77957724586
SN - 0022-1007
VL - 207
SP - 2073
EP - 2079
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 10
ER -