Related Experiment Video

Updated: Aug 11, 2026

Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells
06:55

Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells

Published on: February 22, 2020

N-linked carbohydrate on human leukocyte antigen-C and recognition by natural killer cell inhibitory receptors

E Baba1, R Erskine, J E Boyson

  • 1Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.

Human Immunology
|February 13, 2001
PubMed

Insights

Carbohydrate modifications on HLA-C molecules are crucial for recognition by the inhibitory receptor KIR2DL1. Removing glycosylation significantly impairs this interaction, affecting natural killer cell function.

Area of Science:

  • Immunology
  • Molecular Biology
  • Glycobiology

Background:

  • Natural Killer (NK) cells are critical for innate immunity.
  • NK cell activity is regulated by inhibitory receptors, such as KIR2DL1.
  • HLA-C molecules present antigens to NK cells, influencing their activation or inhibition.

Purpose of the Study:

  • To investigate the role of carbohydrate (glycans) in the interaction between HLA-C and KIR2DL1.
  • To determine if glycosylation of HLA-C is essential for KIR2DL1 binding and function.

Main Methods:

  • Generated cell lines expressing wild-type or non-glycosylated mutant HLA-Cw4 and HLA-Cw6.
  • Utilized KIR2DL1-Ig fusion protein to assess binding to HLA-C transfectants.
  • Employed functional assays measuring inhibitory signaling in NK cell lines (YTS and BW) transfected with KIR2DL1.

Main Results:

  • Binding of KIR2DL1-Ig to HLA-C transfectants was significantly reduced on non-glycosylated mutants.
  • Impaired ability of non-glycosylated HLA-C mutants to induce inhibitory signals in KIR2DL1-expressing NK cells.
  • Mutant HLA-Cw4 and -Cw6 molecules showed reduced signal transduction in a chimeric KIR2DL1-CD3 zeta chain assay.

Conclusions:

  • N-linked glycosylation of HLA-C molecules is essential for recognition by the inhibitory receptor KIR2DL1.
  • The absence of glycosylation dramatically reduces KIR2DL1-mediated inhibition of NK cell activity.
  • Glycosylation plays a critical role in modulating immune responses by influencing HLA-C and KIR2DL1 interactions.

More Related Videos

Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies09:54

Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies

Published on: May 22, 2020

Two Flow Cytometric Approaches of NKG2D Ligand Surface Detection to Distinguish Stem Cells from Bulk Subpopulations in Acute Myeloid Leukemia05:24

Two Flow Cytometric Approaches of NKG2D Ligand Surface Detection to Distinguish Stem Cells from Bulk Subpopulations in Acute Myeloid Leukemia

Published on: February 21, 2021

Related Concept Videos

Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
Antigen Processing Pathways01:31

Antigen Processing Pathways

MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
MHC Class I: Presenting Endogenous...
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...