Related Experiment Video
Updated: Aug 9, 2026
08:49
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Stealth cells: prevention of major histocompatibility complex class II-mediated T-cell activation by cell surface
K L Murad1, E J Gosselin, J W Eaton
1Division of Experimental Pathology, Department of Microbiology and Immunology, Albany Medical College, Albany, NY, USA.
Blood
|September 9, 1999
Summary
Methoxy(polyethylene glycol) (mPEG) modification of peripheral blood mononuclear cells (PBMC) effectively inhibits T-cell proliferation and immune responses. This approach prevents graft-versus-host disease (GVHD) by reducing cell-cell interactions crucial for immune recognition.
Area of Science:
- Immunology
- Biotechnology
- Cell Biology
Background:
- Allogeneic T-cell transfusions/transplants can cause immune responses, including graft-versus-host disease (GVHD) in immunocompromised patients.
- Previous research showed methoxy(polyethylene glycol) (mPEG) attenuated immune recognition of red blood cells.
- This study investigated if mPEG modification could prevent T-cell activation by foreign antigens.
Purpose of the Study:
- To determine if mPEG modification of peripheral blood mononuclear cells (PBMC) can inhibit T-cell activation and proliferation.
- To assess the impact of mPEG modification on cell viability and responsiveness to stimuli.
- To elucidate the mechanisms by which mPEG affects T-cell and antigen-presenting cell (APC) interactions.
Main Methods:
- Mixed lymphocyte reactions (MLR) using HLA class II disparate donor PBMC.
- Quantification of T-cell proliferation via (3)H-thymidine incorporation.
- Assessment of cell viability and response to phytohemagglutinin (PHA) and interleukin-2 (IL-2).
- Flow cytometry to analyze cell surface molecule expression and antibody recognition.
Main Results:
- mPEG modification of PBMC dose-dependently inhibited T-cell proliferation in MLR, with significant reduction (>75% at 0.4 mmol/L mPEG).
- mPEG treatment did not cause cytotoxicity or cellular anergy, as evidenced by normal viability and PHA/IL-2 responses.
- Flow cytometry revealed mPEG significantly decreased recognition of key T-cell (CD2, CD3, CD4, CD8, CD28, CD11a, CD62L) and APC (CD80, CD58, CD62L) molecules involved in cell-cell interactions.
Conclusions:
- mPEG modification is a potent strategy to inhibit T-cell proliferation and immune responses in vitro.
- The mechanism involves steric hindrance of critical cell surface molecules, preventing essential adhesion and costimulatory events.
- mPEG modification of immune cells holds promise for preventing GVHD and other allogeneic immune reactions.
More Related Videos
Related Concept Videos
01:40Cell-mediated Immune Responses
Overview
01:28Cells 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...
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...
01:26Antigens 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.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
01:31Antigen 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...
MHC Class I: Presenting Endogenous...
01:22T 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...
Naive T cells that have not yet encountered an antigen express two primary CD...
01:27Cytotoxic 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...
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...