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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...
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.
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Cell-mediated Immune Responses

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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...
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...
Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...

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Related Experiment Video

Updated: Jun 25, 2026

Examination of Thymic Positive and Negative Selection by Flow Cytometry
14:29

Examination of Thymic Positive and Negative Selection by Flow Cytometry

Published on: October 8, 2012

MerTK regulates thymic selection of autoreactive T cells.

Mark A Wallet1, Rafael R Flores, Yaming Wang

  • 1Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599-7020, USA.

Proceedings of the National Academy of Sciences of the United States of America
|March 3, 2009
PubMed
Summary

Mer tyrosine kinase (MerTK) deficiency in nonobese diabetic mice prevents type 1 diabetes by enhancing thymic negative selection of self-reactive T cells. This highlights MerTK

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Area of Science:

  • Immunology
  • Autoimmunity
  • Endocrinology

Background:

  • T cell-mediated autoimmune diseases, like type 1 diabetes (T1D), are linked to inadequate negative selection of self-reactive thymocytes in the thymus.
  • The precise regulatory mechanisms governing thymic negative selection remain incompletely understood.

Purpose of the Study:

  • To investigate the role of Mer tyrosine kinase (MerTK) in regulating thymic negative selection and its impact on the development of type 1 diabetes.
  • To elucidate the cellular and molecular mechanisms by which MerTK influences T cell autoimmunity against pancreatic beta cells.

Main Methods:

  • Utilized nonobese diabetic (NOD) mice with targeted MerTK gene deletion (Mer(-/-)).
  • Generated bone marrow chimeric mice to assess the cell-intrinsic role of MerTK.
  • Performed fetal thymic organ cultures and administered self-peptides to evaluate thymic negative selection.
  • Analyzed thymic dendritic cell (DC) function in vitro for their capacity to induce thymocyte apoptosis.

Main Results:

  • NOD mice lacking MerTK expression (Mer(-/-)) exhibited significantly reduced pancreatic islet inflammation and failed to develop diabetes.
  • MerTK deficiency led to a decreased frequency of beta cell-specific T cells, independent of other immunoregulatory pathways.
  • Bone marrow chimera studies confirmed that hematopoietic-derived cells lacking MerTK were crucial for preventing beta cell autoimmunity.
  • Mer(-/-) mice showed enhanced thymic negative selection, evidenced by fetal thymic organ cultures and self-peptide administration.
  • Thymic DCs from Mer(-/-) mice demonstrated an augmented ability to induce peptide-specific thymocyte apoptosis in vitro.

Conclusions:

  • MerTK plays a critical role in regulating thymocyte negative selection within the thymus.
  • MerTK-deficient thymic dendritic cells exhibit an enhanced capacity to eliminate self-reactive T cells.
  • These findings reveal a novel mechanism of MerTK-mediated control over T cell autoimmunity and suggest MerTK as a potential therapeutic target for type 1 diabetes.