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Related Concept Videos

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...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
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...

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Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
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Partial MHC class II constructs inhibit MIF/CD74 binding and downstream effects.

Gil Benedek1, Roberto Meza-Romero, Shayne Andrew

  • 1Department of Veterans Affairs Medical Center, Neuroimmunology Research, Portland, OR 97239, USA.

European Journal of Immunology
|April 12, 2013
PubMed
Summary
This summary is machine-generated.

Recombinant T-cell receptor ligands (RTLs) targeting CD74 inhibit macrophage migration inhibitory factor (MIF) by blocking its binding and reducing cell-surface expression. This dual action reverses inflammation in experimental autoimmune encephalomyelitis (EAE).

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Related Experiment Videos

Last Updated: May 12, 2026

Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
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Published on: February 28, 2019

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Simultaneous Quantification of Anti-vector and Anti-transgene-Specific CD8+ T Cells Via MHC I Tetramer Staining After Vaccination with a Viral Vector
08:10

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

Area of Science:

  • Immunology
  • Molecular Biology
  • Neuroscience

Background:

  • Macrophage migration inhibitory factor (MIF) and its receptor CD74 are key regulators of immune responses.
  • Dysregulation of the MIF/CD74 pathway contributes to inflammatory diseases like multiple sclerosis (MS).
  • Current therapeutic strategies often target individual components of inflammatory pathways.

Purpose of the Study:

  • To investigate the potential of partial MHC class II constructs, termed recombinant T-cell receptor ligands (RTLs), as inhibitors of MIF activity.
  • To explore the mechanism by which RTLs modulate the MIF/CD74 interaction and its downstream effects.
  • To assess the therapeutic efficacy of RTLs in preclinical models of neuroinflammation and in relevant human cell types.

Main Methods:

  • Development of partial MHC class II constructs (RTLs) with linked β1α1 domains and covalently attached antigenic peptides.
  • Assays to measure the binding of recombinant human MIF (rhMIF) to immunopurified CD74.
  • Flow cytometry to assess CD74 cell-surface expression on monocytes.
  • In vivo studies using experimental autoimmune encephalomyelitis (EAE) models in mice.
  • Analysis of downstream MIF effects, including cytokine secretion, apoptosis, and cell migration.

Main Results:

  • RTLs effectively blocked rhMIF binding to CD74 and downregulated CD74 cell-surface expression.
  • This bifunctional inhibition abrogated MIF-mediated pro-inflammatory cytokine secretion, anti-apoptotic activity, and migration inhibition.
  • RTL treatment reversed clinical and histological signs of EAE.
  • Humanized RTLs reduced CD74 expression on monocytes from EAE mice and MS patients, decreasing MIF binding.

Conclusions:

  • Partial MHC class II constructs (RTLs) represent a novel bifunctional therapeutic strategy targeting the MIF/CD74 axis.
  • RTLs inhibit MIF activity by simultaneously blocking CD74 accessibility and availability, leading to potent anti-inflammatory effects.
  • RTLs demonstrate potential for treating inflammatory conditions, including neuroinflammatory diseases like MS, by modulating immune cell function.