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T Cell Activation and Clonal Selection

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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Related Experiment Video

Updated: Mar 15, 2026

Examination of Thymic Positive and Negative Selection by Flow Cytometry

Examination of Thymic Positive and Negative Selection by Flow Cytometry

Published on: October 8, 2012

SHP1-ing thymic selection.

Nicholas R J Gascoigne¹, Joanna Brzostek², Monika Mehta²

¹Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. micnrjg@nus.edu.sg.

European Journal of Immunology

|September 8, 2016

Summary

Src homology region 2 domain-containing phosphatase-1 (SHP1) negatively regulates T-cell receptor (TCR) signaling. SHP1 deficiency in thymocytes impairs T-cell maturation and survival, highlighting its critical role in thymic development.

Keywords:

Phosphatase Signal transduction T cell Thymic selection

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Area of Science:

Immunology
Cell Biology
Molecular Biology

Background:

T-cell receptor (TCR) signal strength is crucial for thymocyte development and T-cell function.
SHP1, a tyrosine phosphatase, acts as a negative regulator of TCR signaling.
Previous studies on SHP1's role in thymic development yielded conflicting results.

Purpose of the Study:

To investigate the role of SHP1 in thymocyte development and TCR signal regulation using conditional knockout mice.
To clarify the impact of SHP1 deficiency on T-cell maturation and survival.

Main Methods:

Utilized SHP1 conditional knockout mice to study thymocyte development.
Analyzed TCR signal transduction in thymocytes post-positive selection.
Assessed cell death in response to TCR ligands.

Main Results:

SHP1 deficiency leads to impaired thymocyte development with a loss of mature, post-selection cells.
Increased TCR signal transduction was observed in SHP1-deficient thymocytes immediately after positive selection.
SHP1-deficient thymocytes exhibited increased cell death upon encountering weak TCR ligands.

Conclusions:

SHP1 plays a significant role in the negative regulation of TCR signal strength during thymocyte positive selection.
SHP1 deficiency results in developmental defects and cell loss, similar to Themis deficiency.
SHP1 is essential for the final maturation of single positive thymocytes.