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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: May 2, 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

Natural polymorphisms in Tap2 influence negative selection and CD4∶CD8 lineage commitment in the rat.

Jonatan Tuncel¹, Sabrina Haag¹, Anthony C Y Yau¹

¹Section for Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

|March 4, 2014

Summary

Genetic variation within the rat Major Histocompatibility Complex (MHC) influences T cell development. A specific recombination event between RT1-A and Tap2 genes impacts T cell selection and CD4:CD8 ratios.

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Last Updated: May 2, 2026

Examination of Thymic Positive and Negative Selection by Flow Cytometry

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Published on: October 8, 2012

Preparation and Applications of Organotypic Thymic Slice Cultures

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Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets

Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets

Published on: April 16, 2015

Area of Science:

Immunology
Genetics
Molecular Biology

Background:

The Major Histocompatibility Complex (MHC) plays a crucial role in immune responses and T cell development.
Genetic variation within the MHC influences T cell lineage commitment (CD4:CD8 ratio) and MHC expression.
The specific genes responsible for these effects within the MHC remain largely unresolved.

Purpose of the Study:

To investigate the impact of natural genetic variation on MHC expression and CD4:CD8 lineage commitment in rats.
To identify specific genes within the MHC responsible for regulating T cell selection and MHC expression.

Main Methods:

Utilized two genetic models in rats: outbred Heterogeneous Stock rats and MHC-recombinant congenic strains.
Mapped Quantitative Trait Loci (QTLs) associated with MHC protein expression and CD4:CD8 T cell ratios.
Generated congenic strains to refine QTLs and identify candidate genes.

Main Results:

Identified 10 QTLs, with several localizing to the MHC region.
Refined QTLs to two adjacent intervals, implicating the transporter associated with antigen processing 2 (Tap2) and classical MHC class I genes (RT1-A).
An interaction between RT1-A and Tap2, revealed by a rare recombination event, affected MHC class I expression, negative selection, and CD8 T cell lineage commitment.

Conclusions:

A recombination between RT1-A and Tap2 in rats alters the peptide repertoire presented by MHC class I molecules.
This restricted peptide presentation leads to reduced negative selection of CD8 single-positive thymocytes.
This study demonstrates how genetic recombination within the MHC influences T cell lineage commitment.