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NKp44/HLA-DP-dependent regulation of CD8 effector T cells by NK cells

  1. Author:
    Padoan, Benedetta
    Casar, Christian
    Krause, Jenny
    Schultheiss, Christoph
    Baumdick, Martin E
    Niehrs, Annika
    Zecher, Britta F
    Pujantell, Maria
    Yuki,Yuko
    Martin,Pat
    Remmerswaal, Ester B M
    Dekker, Tamara
    van der Bom-Baylon, Nelly D
    Noble, Janelle A
    Carrington,Mary
    Bemelman, Frederike J
    van Lier, Rene A W
    Binder, Mascha
    Gagliani, Nicola
    Bunders, Madeleine J
    Altfeld, Marcus

  2. Author Address

    Research Department Virus Immunology, Leibniz Institute of Virology, 20251 Hamburg, Germany., Bioinformatics Core, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; Center for Immunology, University of Minnesota, Minneapolis, MN, USA., Division of Medical Oncology, University Hospital Basel, 4031 Basel, Switzerland; Laboratory of Translational Immuno-Oncology, Department of Biomedicine, University and University Hospital Basel, 4031 Basel, Switzerland., Research Department Virus Immunology, Leibniz Institute of Virology, 20251 Hamburg, Germany; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Research Department Virus Immunology, Leibniz Institute of Virology, 20251 Hamburg, Germany; I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA; Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA., Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Department of Pediatrics UCSF, Children 39;s Hospital Oakland Research Institute, Oakland, CA 94609, USA., Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA; Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Renal Transplant Unit, Division of Internal Medicine, Academic Medical Centre, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., University Medical Center Utrecht, Utrecht, the Netherlands., I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; Hamburg Center for Translational Immunology (HCTI), Hamburg, Germany., Research Department Virus Immunology, Leibniz Institute of Virology, 20251 Hamburg, Germany; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; Hamburg Center for Translational Immunology (HCTI), Hamburg, Germany., Research Department Virus Immunology, Leibniz Institute of Virology, 20251 Hamburg, Germany; Hamburg Center for Translational Immunology (HCTI), Hamburg, Germany. Electronic address: marcus.altfeld@leibniz-liv.de.,
    1. Year: 2024
    2. Date: Apr 12
    3. Epub Date: 2024 04 12
  2. Journal: Cell Reports
    1. 43
    2. 4
    3. Pages: 114089
  4. Type of Article: Article
  5. Article Number: 114089
  1. Abstract:

    Although natural killer (NK) cells are recognized for their modulation of immune responses, the mechanisms by which human NK cells mediate immune regulation are unclear. Here, we report that expression of human leukocyte antigen (HLA)-DP, a ligand for the activating NK cell receptor NKp44, is significantly upregulated on CD8+ effector T cells, in particular in human cytomegalovirus (HCMV)+ individuals. HLA-DP+ CD8+ T cells expressing NKp44-binding HLA-DP antigens activate NKp44+ NK cells, while HLA-DP+ CD8+ T cells not expressing NKp44-binding HLA-DP antigens do not. In line with this, frequencies of HLA-DP+ CD8+ T cells are increased in individuals not encoding for NKp44-binding HLA-DP haplotypes, and contain hyper-expanded CD8+ T cell clones, compared to individuals expressing NKp44-binding HLA-DP molecules. These findings identify a molecular interaction facilitating the HLA-DP haplotype-specific editing of HLA-DP+ CD8+ T cell effector populations by NKp44+ NK cells and preventing the generation of hyper-expanded T cell clones, which have been suggested to have increased potential for autoimmunity. Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

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  2. DOI: 10.1016/j.celrep.2024.114089
  3. PMID: 38615318
  4. PII : S2211-1247(24)00417-0

Library Notes

  1. Fiscal Year: FY2023-2024
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