Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1
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Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1. / Garcia-Beltran, Wilfredo F; Hölzemer, Angelique; Martrus, Gloria; Chung, Amy W; Pacheco, Yovana; Simoneau, Camille R; Rucevic, Marijana; Lamothe-Molina, Pedro A; Pertel, Thomas; Kim, Tae-Eun; Dugan, Haley; Alter, Galit; Dechanet-Merville, Julie; Jost, Stephanie; Carrington, Mary; Altfeld, Marcus.
In: NAT IMMUNOL, Vol. 17, No. 9, 09.2016, p. 1067-74.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1
AU - Garcia-Beltran, Wilfredo F
AU - Hölzemer, Angelique
AU - Martrus, Gloria
AU - Chung, Amy W
AU - Pacheco, Yovana
AU - Simoneau, Camille R
AU - Rucevic, Marijana
AU - Lamothe-Molina, Pedro A
AU - Pertel, Thomas
AU - Kim, Tae-Eun
AU - Dugan, Haley
AU - Alter, Galit
AU - Dechanet-Merville, Julie
AU - Jost, Stephanie
AU - Carrington, Mary
AU - Altfeld, Marcus
PY - 2016/9
Y1 - 2016/9
N2 - The activating natural killer (NK)-cell receptor KIR3DS1 has been linked to the outcome of various human diseases, including delayed progression of disease caused by human immunodeficiency virus type 1 (HIV-1), yet a ligand that would account for its biological effects has remained unknown. We screened 100 HLA class I proteins and found that KIR3DS1 bound to HLA-F, a result we confirmed biochemically and functionally. Primary human KIR3DS1(+) NK cells degranulated and produced antiviral cytokines after encountering HLA-F and inhibited HIV-1 replication in vitro. Activation of CD4(+) T cells triggered the transcription and surface expression of HLA-F mRNA and HLA-F protein, respectively, and induced binding of KIR3DS1. HIV-1 infection further increased the transcription of HLA-F mRNA but decreased the binding of KIR3DS1, indicative of a mechanism for evading recognition by KIR3DS1(+) NK cells. Thus, we have established HLA-F as a ligand of KIR3DS1 and have demonstrated cell-context-dependent expression of HLA-F that might explain the widespread influence of KIR3DS1 in human disease.
AB - The activating natural killer (NK)-cell receptor KIR3DS1 has been linked to the outcome of various human diseases, including delayed progression of disease caused by human immunodeficiency virus type 1 (HIV-1), yet a ligand that would account for its biological effects has remained unknown. We screened 100 HLA class I proteins and found that KIR3DS1 bound to HLA-F, a result we confirmed biochemically and functionally. Primary human KIR3DS1(+) NK cells degranulated and produced antiviral cytokines after encountering HLA-F and inhibited HIV-1 replication in vitro. Activation of CD4(+) T cells triggered the transcription and surface expression of HLA-F mRNA and HLA-F protein, respectively, and induced binding of KIR3DS1. HIV-1 infection further increased the transcription of HLA-F mRNA but decreased the binding of KIR3DS1, indicative of a mechanism for evading recognition by KIR3DS1(+) NK cells. Thus, we have established HLA-F as a ligand of KIR3DS1 and have demonstrated cell-context-dependent expression of HLA-F that might explain the widespread influence of KIR3DS1 in human disease.
KW - Journal Article
U2 - 10.1038/ni.3513
DO - 10.1038/ni.3513
M3 - SCORING: Journal article
C2 - 27455421
VL - 17
SP - 1067
EP - 1074
JO - NAT IMMUNOL
JF - NAT IMMUNOL
SN - 1529-2908
IS - 9
ER -