HIV-1-Mediated Downmodulation of HLA-C Impacts Target Cell Recognition and Antiviral Activity of NK Cells

Christian Körner, Camille R. Simoneau, Philipp Schommers, Mitchell Granoff, Maja Ziegler, Angelique Hölzemer, Sebastian Lunemann, Janet Chukwukelu, Björn Corleis, Vivek Naranbhai, Douglas S. Kwon, Eileen Scully, Stephanie Jost, Frank Kirchhoff, Mary Carrington, Marcus Altfeld

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)111-119.e4
JournalCell Host and Microbe
Volume22
Issue number1
DOIs
StatePublished - Jul 12 2017

Keywords

  • HIV-1
  • HLA class I
  • HLA-C
  • KIR
  • natural killer cells
  • NK cells

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology and Microbiology(all)
  • Cancer Research

Fingerprint Dive into the research topics of 'HIV-1-Mediated Downmodulation of HLA-C Impacts Target Cell Recognition and Antiviral Activity of NK Cells'. Together they form a unique fingerprint.

  • Cite this

    Körner, C., Simoneau, C. R., Schommers, P., Granoff, M., Ziegler, M., Hölzemer, A., Lunemann, S., Chukwukelu, J., Corleis, B., Naranbhai, V., Kwon, D. S., Scully, E., Jost, S., Kirchhoff, F., Carrington, M., & Altfeld, M. (2017). HIV-1-Mediated Downmodulation of HLA-C Impacts Target Cell Recognition and Antiviral Activity of NK Cells. Cell Host and Microbe, 22(1), 111-119.e4. https://doi.org/10.1016/j.chom.2017.06.008