Faculty Opinions recommendation of HLA-F and MHC class I open conformers are ligands for NK cell Ig-like receptors.

2014 ◽  
Author(s):  
Ronald Bontrop
Keyword(s):  
Mhc Class I ◽  
Nk Cell ◽  
Class I

scholarly journals ERAP1 Controls the Interaction of the Inhibitory Receptor KIR3DL1 With HLA-B51:01 by Affecting Natural Killer Cell Function

2021 ◽  
Vol 12 ◽  
Author(s):  
Silvia D’Amico ◽  
Valerio D’Alicandro ◽  
Mirco Compagnone ◽  
Patrizia Tempora ◽  
Giusy Guida ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Cell Function ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Subset ◽  
Human Tumor ◽  
Hla Class I ◽  
Class I ◽  
Pharmacological Inhibition ◽  
Mhc Class I Molecules

The endoplasmic reticulum aminopeptidase ERAP1 regulates innate and adaptive immune responses by trimming peptides for presentation by major histocompatibility complex (MHC) class I molecules. Previously, we have shown that genetic or pharmacological inhibition of ERAP1 on murine and human tumor cell lines perturbs the engagement of NK cell inhibitory receptors Ly49C/I and Killer-cell Immunoglobulin-like receptors (KIRs), respectively, by their specific ligands (MHC class I molecules), thus leading to NK cell killing. However, the effect of ERAP1 inhibition in tumor cells was highly variable, suggesting that its efficacy may depend on several factors, including MHC class I typing. To identify MHC class I alleles and KIRs that are more sensitive to ERAP1 depletion, we stably silenced ERAP1 expression in human HLA class I-negative B lymphoblastoid cell line 721.221 (referred to as 221) transfected with a panel of KIR ligands (i.e. HLA-B*51:01, -Cw3, -Cw4 and -Cw7), or HLA-A2 which does not bind any KIR, and tested their ability to induce NK cell degranulation and cytotoxicity. No change in HLA class I surface expression was detected in all 221 transfectant cells after ERAP1 depletion. In contrast, CD107a expression levels were significantly increased on NK cells stimulated with 221-B*51:01 cells lacking ERAP1, particularly in the KIR3DL1-positive NK cell subset. Consistently, genetic or pharmacological inhibition of ERAP1 impaired the recognition of HLA-B*51:01 by the YTS NK cell overexpressing KIR3DL1*001, suggesting that ERAP1 inhibition renders HLA-B*51:01 molecules less eligible for binding to KIR3DL1. Overall, these results identify HLA-B*51:01/KIR3DL1 as one of the most susceptible combinations for ERAP1 inhibition, suggesting that individuals carrying HLA-B*51:01-like antigens may be candidates for immunotherapy based on pharmacological inhibition of ERAP1.

scholarly journals Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies

Blood ◽  
2014 ◽  
Vol 123 (5) ◽  
pp. 678-686 ◽  
Author(s):  
Holbrook E. Kohrt ◽  
Ariane Thielens ◽  
Aurelien Marabelle ◽  
Idit Sagiv-Barfi ◽  
Caroline Sola ◽  
...  
Keyword(s):  
Natural Killer Cells ◽  
Natural Killer ◽  
Mhc Class I ◽  
Nk Cell ◽  
Class I ◽  
Lymphoma Cells ◽  
Killer Cells ◽  
Key Points ◽  
Anti Cd20 ◽  
Cd20 Antibodies

Key Points Blockade of inhibitory KIRs with MHC class I antigens on lymphoma cells by anti-KIR antibodies augments NK-cell spontaneous cytotoxicity. In combination with anti-CD20 mAbs, anti-KIR induces enhanced NK cell–mediated, rituximab-dependent cytotoxicity against lymphoma.

scholarly journals Detection of major histocompatibility complex class I-restricted, HIV- specific cytotoxic T lymphocytes in the blood of infected hemophiliacs

Blood ◽  
1989 ◽  
Vol 73 (7) ◽  
pp. 1909-1914 ◽  
Author(s):  
RA Koup ◽  
JL Sullivan ◽  
PH Levine ◽  
D Brettler ◽  
A Mahr ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Mhc Class I ◽  
Cytotoxic T Lymphocytes ◽  
Mononuclear Cells ◽  
Nk Cell ◽  
Class I ◽  
Gene Products ◽  
Major Histocompatibility ◽  
Peripheral Blood Mononuclear ◽  
Hiv 1

Abstract Major histocompatibility (MHC)-restricted, human immunodeficiency virus type one (HIV-1)-specific, cytotoxic T lymphocytes (CTLs) were detected in the peripheral blood mononuclear cells (PBMCs) of HIV-1-infected individuals. Using a system of autologous B and T lymphoblastoid cell lines infected with recombinant vaccinia vectors (VVs) expressing HIV-1 gene products, we were able to detect HIV-1-specific cytolytic responses in the PBMCs of 88% of HIV-1-seropositive hemophiliac patients in the absence of in vitro stimulation. These cytolytic responses were directed against both HIV-1 envelope and gag gene products. The responses were resistant to natural killer (NK) cell depletion and were inhibited by monoclonal antibodies (MoAbs) to the T cell receptor, CD8 surface antigens, and MHC class I antigens, suggesting a classical MHC class I restricted, virus-specific CTL response.

scholarly journals A New Mechanism of NK Cell Cytotoxicity Activation: The CD40–CD40 Ligand Interaction

1997 ◽  
Vol 185 (12) ◽  
pp. 2053-2060 ◽  
Author(s):  
Ennio Carbone ◽  
Giuseppina Ruggiero ◽  
Giuseppe Terrazzano ◽  
Carmen Palomba ◽  
Ciro Manzo ◽  
...  
Keyword(s):  
Nk Cells ◽  
Mhc Class I ◽  
Nk Cell ◽  
Cd40 Ligand ◽  
Class I ◽  
Target Cells ◽  
Ligand Interaction ◽  
Effector Functions ◽  
Nk Cell Cytotoxicity ◽  
Dependent Pathway

NK recognition is regulated by a delicate balance between positive signals initiating their effector functions, and inhibitory signals preventing them from proceeding to cytolysis. Knowledge of the molecules responsible for positive signaling in NK cells is currently limited. We demonstrate that IL-2–activated human NK cells can express CD40 ligand (CD40L) and that recognition of CD40 on target cells can provide an activation pathway for such human NK cells. CD40-transfected P815 cells were killed by NK cell lines expressing CD40L, clones and PBLderived NK cells cultured for 18 h in the presence of IL-2, but not by CD40L-negative fresh NK cells. Cross-linking of CD40L on IL-2–activated NK cells induced redirected cytolysis of CD40-negative but Fc receptor-expressing P815 cells. The sensitivity of human TAP-deficient T2 cells could be blocked by anti-CD40 antibodies as well as by reconstitution of TAP/MHC class I expression, indicating that the CD40-dependent pathway for NK activation can be downregulated, at least in part, by MHC class I molecules on the target cells. NK cell recognition of CD40 may be important in immunoregulation as well as in immune responses against B cell malignancies.

scholarly journals Viral MHC Class I–like Molecule Allows Evasion of NK Cell Effector Responses In Vivo

2014 ◽  
Vol 193 (12) ◽  
pp. 6061-6069 ◽  
Author(s):  
Michal Pyzik ◽  
Anne A. Dumaine ◽  
Benoît Charbonneau ◽  
Nassima Fodil-Cornu ◽  
Stipan Jonjic ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Nk Cell ◽  
Class I ◽  
Cell Effector

scholarly journals P10-01. MHC class I chain-related protein A shedding in chronic HIV-1 infection is associated with profound NK cell dysfunction

Retrovirology ◽  
2009 ◽  
Vol 6 (S3) ◽  
Author(s):  
A Nolting ◽  
R Luteijn ◽  
A Dugast ◽  
M Carrington ◽  
S Rihn ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Nk Cell ◽  
Protein A ◽  
Class I ◽  
Related Protein ◽  
Cell Dysfunction ◽  
Hiv 1

scholarly journals An Essential Role for Tumor Necrosis Factor in Natural Killer Cell–mediated Tumor Rejection in the Peritoneum

1998 ◽  
Vol 188 (9) ◽  
pp. 1611-1619 ◽  
Author(s):  
Mark J. Smyth ◽  
Janice M. Kelly ◽  
Alan G. Baxter ◽  
Heinrich Körner ◽  
Jonathon D. Sedgwick
Keyword(s):  
Tumor Necrosis Factor ◽  
Nk Cells ◽  
Natural Killer ◽  
Mhc Class I ◽  
Tumor Necrosis ◽  
Nk Cell ◽  
Tumor Rejection ◽  
Class I ◽  
Deficient Mice ◽  
Necrosis Factor

Natural killer (NK) cells are thought to provide the first line of defence against tumors, particularly major histocompatibility complex (MHC) class I− variants. We have confirmed in C57BL/6 (B6) mice lacking perforin that peritoneal growth of MHC class I− RMA-S tumor cells in unprimed mice is controlled by perforin-dependent cytotoxicity mediated by CD3− NK1.1+ cells. Furthermore, we demonstrate that B6 mice lacking tumor necrosis factor (TNF) are also significantly defective in their rejection of RMA-S, despite the fact that RMA-S is insensitive to TNF in vitro and that spleen NK cells from B6 and TNF-deficient mice are equally lytic towards RMA-S. NK cell recruitment into the peritoneum was abrogated in TNF-deficient mice challenged with RMA-S or RM-1, a B6 MHC class I− prostate carcinoma, compared with B6 or perforin-deficient mice. The reduced NK cell migration to the peritoneum of TNF-deficient mice correlated with the defective NK cell response to tumor in these mice. By contrast, a lack of TNF did not affect peptide-specific cytotoxic T lymphocyte–mediated rejection of tumor from the peritoneum of preimmunized mice. Overall, these data show that NK cells delivering perforin are the major effectors of class I− tumor rejection in the peritoneum, and that TNF is specifically critical for their recruitment to the peritoneum.

scholarly journals Cell Surface Organization of Stress-inducible Proteins ULBP and MICA That Stimulate Human NK Cells and T Cells via NKG2D

2004 ◽  
Vol 199 (7) ◽  
pp. 1005-1010 ◽  
Author(s):  
Konstantina Eleme ◽  
Sabrina B. Taner ◽  
Björn Önfelt ◽  
Lucy M. Collinson ◽  
Fiona E. McCann ◽  
...  
Keyword(s):  
Cell Surface ◽  
Nk Cells ◽  
Lipid Rafts ◽  
Mhc Class I ◽  
Fluorescent Protein ◽  
Nk Cell ◽  
Surface Proteins ◽  
Class I ◽  
Immune Synapse ◽  
Green Fluorescent

Cell surface proteins major histocompatibility complex (MHC) class I–related chain A (MICA) and UL16-binding proteins (ULBP) 1, 2, and 3 are up-regulated upon infection or tumor transformation and can activate human natural killer (NK) cells. Patches of cross-linked raft resident ganglioside GM1 colocalized with ULBP1, 2, 3, or MICA, but not CD45. Thus, ULBPs and MICA are expressed in lipid rafts at the cell surface. Western blotting revealed that glycosylphosphatidylinositol (GPI)-anchored ULBP3 but not transmembrane MICA, MHC class I protein, or transferrin receptor, accumulated in detergent-resistant membranes containing GM1. Thus, MICA may have a weaker association with lipid rafts than ULBP3, yet both proteins accumulate at an activating human NK cell immune synapse. Target cell lipid rafts marked by green fluorescent protein–tagged GPI also accumulate with ULBP3 at some synapses. Electron microscopy reveals constitutive clusters of ULBP at the cell surface. Regarding a specific molecular basis for the organization of these proteins, ULBP1, 2, and 3 and MICA are lipid modified. ULBP1, 2, and 3 are GPI anchored, and we demonstrate here that MICA is S-acylated. Finally, expression of a truncated form of MICA that lacks the putative site for S-acylation and the cytoplasmic tail can be expressed at the cell surface, but is unable to activate NK cells.

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