Related Experiment Video

Updated: Aug 9, 2026

HLA-Ig Based Artificial Antigen Presenting Cells for Efficient ex vivo Expansion of Human CTL
07:18

HLA-Ig Based Artificial Antigen Presenting Cells for Efficient ex vivo Expansion of Human CTL

Published on: April 11, 2011

Reduction of CTL antipeptide response mediated by CD8+ cells whose class I MHC can bind the peptide

S R Sambhara1, R G Miller

  • 1Ontario Cancer Institute, Toronto, Canada.

Journal of Immunology (Baltimore, Md. : 1950)
|February 1, 1994
PubMed

Insights

Certain immune cells can suppress T cell responses. This study identifies CD8+ cells as "veto cells" that inhibit T cell activation through a novel signaling pathway, impacting both in vitro and in vivo immune responses.

Area of Science:

  • Immunology
  • Cellular immunology
  • T cell biology

Background:

  • Cytotoxic T lymphocyte (CTL) responses are crucial for adaptive immunity.
  • CTLs recognize peptide antigens presented by MHC class I molecules.
  • Modulation of CTL responses is critical for immune regulation.

Purpose of the Study:

  • To investigate the mechanism of CTL response reduction by added cells in mixed lymphocyte reactions (MLRs).
  • To identify the role of CD8+ cells and peptide binding in suppressing CTL precursors.
  • To explore the potential in vivo relevance of this suppressive mechanism.

Main Methods:

  • In vitro generation of primary CTL responses using peptides and MHC class I.
  • Addition of cells from a 5-day MLR to CTL cultures.
  • Use of anti-Ly-2.1 monoclonal antibody (mAb) to block CD8 signaling.
  • In vivo experiments involving intravenous injection of peptide-pulsed syngeneic lymphoid cells in mice.

Main Results:

  • Addition of CD8+ MLR cells that bind specific peptides significantly reduced primary CTL responses.
  • These CD8+ MLR cells were identified as "veto cells" that deliver a negative signal to CTL precursors.
  • Blocking CD8 signaling with anti-Ly-2.1 mAb partially restored the CTL response.
  • In vivo administration of peptide-pulsed cells specifically reduced subsequent in vitro CTL responses against that peptide.

Conclusions:

  • CD8+ veto cells can actively suppress peptide-specific CTL responses through a CD8-mediated signaling pathway.
  • This veto cell mechanism plays a role in regulating immune responses both in vitro and in vivo.
  • Understanding veto cell function offers insights into immune tolerance and regulation.

More Related Videos

Simultaneous Quantification of Anti-vector and Anti-transgene-Specific CD8+ T Cells Via MHC I Tetramer Staining After Vaccination with a Viral Vector08:10

Simultaneous Quantification of Anti-vector and Anti-transgene-Specific CD8+ T Cells Via MHC I Tetramer Staining After Vaccination with a Viral Vector

Published on: November 28, 2018

Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation12:09

Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation

Published on: February 28, 2019

Related Concept Videos

Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

Overview
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...
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
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...