The carboxy-terminal region of CD5 is required for c-CBL mediated TCR signaling downmodulation in thymocytes

Related Experiment Video

Updated: May 14, 2026

Generation of Human Chimeric Antigen Receptor Regulatory T Cells
10:29

Generation of Human Chimeric Antigen Receptor Regulatory T Cells

Published on: January 3, 2025

Nelly S Roa1, Diana Ordoñez-Rueda, Jesús R Chávez-Rios

  • 1Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, DF 04510, Mexico.

Biochemical and Biophysical Research Communications
|February 5, 2013
PubMed

Insights

CD5 negatively regulates T-cell receptor (TCR) signaling in thymocytes. This study reveals CD5

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • CD5 acts as a negative regulator of T-cell receptor (TCR) signaling during thymocyte development.
  • The ubiquitin ligase c-Cbl is involved in downregulating TCR signaling and associates with CD5.
  • TCR crosslinking induces ubiquitylation and degradation of signaling molecules and CD5.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which CD5 downmodulates TCR signaling.
  • To investigate the role of CD5's carboxy-terminal region and c-Cbl interaction in TCR signal regulation.

Main Methods:

  • Co-engagement of CD3 and CD5 in thymocytes.
  • Analysis of c-Cbl phosphorylation and Vav degradation.
  • Site-directed mutagenesis of CD5, including deletion of the pseudo-ITAM domain.

Main Results:

  • Co-engagement of CD3 and CD5 enhanced c-Cbl phosphorylation in an ITAM-independent manner.
  • The carboxy-terminal region of CD5, not the pseudo-ITAM domain, was crucial for c-Cbl phosphorylation.
  • CD5's carboxy-terminal region was essential for Vav degradation, a c-Cbl target.

Conclusions:

  • The distal cytoplasmic domain of CD5, including Y463, plays a significant role in downmodulating TCR signals.
  • This downmodulation occurs via interaction with c-Cbl, independent of CD5's pseudo-ITAM domain.
  • CD5 utilizes c-Cbl-mediated ubiquitylation pathways to regulate TCR signaling during thymocyte development.

More Related Videos

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Related Concept Videos

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...
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 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...
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...