HIV-1-Mediated Downmodulation of HLA-C Impacts Target Cell Recognition and Antiviral Activity of NK Cells
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HIV-1-Mediated Downmodulation of HLA-C Impacts Target Cell Recognition and Antiviral Activity of NK Cells. / Körner, Christian; Simoneau, Camille R; Schommers, Philipp; Granoff, Mitchell; Ziegler, Maja; Hölzemer, Angelique; Lunemann, Sebastian; Chukwukelu, Janet; Corleis, Björn; Naranbhai, Vivek; Kwon, Douglas S; Scully, Eileen P; Jost, Stephanie; Kirchhoff, Frank; Carrington, Mary; Altfeld, Marcus.
in: CELL HOST MICROBE, Jahrgang 22, Nr. 1, 12.07.2017, S. 111-119.e4.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - HIV-1-Mediated Downmodulation of HLA-C Impacts Target Cell Recognition and Antiviral Activity of NK Cells
AU - Körner, Christian
AU - Simoneau, Camille R
AU - Schommers, Philipp
AU - Granoff, Mitchell
AU - Ziegler, Maja
AU - Hölzemer, Angelique
AU - Lunemann, Sebastian
AU - Chukwukelu, Janet
AU - Corleis, Björn
AU - Naranbhai, Vivek
AU - Kwon, Douglas S
AU - Scully, Eileen P
AU - Jost, Stephanie
AU - Kirchhoff, Frank
AU - Carrington, Mary
AU - Altfeld, Marcus
N1 - Copyright © 2017 Elsevier Inc. All rights reserved.
PY - 2017/7/12
Y1 - 2017/7/12
N2 - It was widely accepted that HIV-1 downregulates HLA-A/B to avoid CTL recognition while leaving HLA-C unaltered in order to prevent NK cell activation by engaging inhibitory NK cell receptors, but it was recently observed that most primary isolates of HIV-1 can mediate HLA-C downmodulation. Now we report that HIV-1-mediated downmodulation of HLA-C was associated with reduced binding to its respective inhibitory receptors. Despite this, HLA-C-licensed NK cells displayed reduced antiviral activity compared to their unlicensed counterparts, potentially due to residual binding to the respective inhibitory receptors. Nevertheless, NK cells were able to sense alterations of HLA-C expression demonstrated by increased antiviral activity when exposed to viral strains with differential abilities to downmodulate HLA-C. These results suggest that the capability of HLA-C-licensed NK cells to control HIV-1 replication is determined by the strength of KIR/HLA-C interactions and is thus dependent on both host genetics and the extent of virus-mediated HLA-C downregulation.
AB - It was widely accepted that HIV-1 downregulates HLA-A/B to avoid CTL recognition while leaving HLA-C unaltered in order to prevent NK cell activation by engaging inhibitory NK cell receptors, but it was recently observed that most primary isolates of HIV-1 can mediate HLA-C downmodulation. Now we report that HIV-1-mediated downmodulation of HLA-C was associated with reduced binding to its respective inhibitory receptors. Despite this, HLA-C-licensed NK cells displayed reduced antiviral activity compared to their unlicensed counterparts, potentially due to residual binding to the respective inhibitory receptors. Nevertheless, NK cells were able to sense alterations of HLA-C expression demonstrated by increased antiviral activity when exposed to viral strains with differential abilities to downmodulate HLA-C. These results suggest that the capability of HLA-C-licensed NK cells to control HIV-1 replication is determined by the strength of KIR/HLA-C interactions and is thus dependent on both host genetics and the extent of virus-mediated HLA-C downregulation.
KW - Journal Article
U2 - 10.1016/j.chom.2017.06.008
DO - 10.1016/j.chom.2017.06.008
M3 - SCORING: Journal article
C2 - 28704647
VL - 22
SP - 111-119.e4
JO - CELL HOST MICROBE
JF - CELL HOST MICROBE
SN - 1931-3128
IS - 1
ER -