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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: Jun 5, 2025

Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates

Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates

Published on: May 9, 2025

T-Switch: A specificity-based engineering platform for developing safe and effective T cell therapeutics.

Nouran S Abdelfattah¹, Tomasz Kula¹, Stephen J Elledge¹

¹Department of Genetics, Harvard Medical School, Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

|December 4, 2024

Summary

This summary is machine-generated.

A new platform called T-Switch engineers T-cell receptors (TCRs) to target self-antigens for adoptive T-cell therapy (ACT). This approach bypasses natural tolerance, creating potent and safe T-cell therapeutics for cancer treatment.

Keywords:

T cells TCR evolution epitope specificity self-reactivity

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Published on: August 9, 2019

Area of Science:

Immunology
Biotechnology
Oncology

Background:

Adoptive T-cell therapy (ACT) faces challenges targeting self-antigens due to T-cell tolerance mechanisms.
Self-reactive T-cells are typically eliminated or become regulatory, limiting their therapeutic use against self-antigens.
Developing T-cell therapies that safely target tumor-associated self-antigens is crucial for cancer treatment.

Purpose of the Study:

To develop an in vitro platform, T-Switch, for engineering T-cell receptors (TCRs) capable of targeting self-antigens.
To create, modify, and profile synthetic TCRs for enhanced T-cell-based immunotherapies.
To generate potent and safe T-cell therapeutics by overcoming T-cell tolerance to self-antigens.

Main Methods:

The T-Switch platform expands T-cells recognizing a foreign peptide antigen.
Directed evolution modifies the TCR's peptide-binding region to switch specificity to a target self-antigen.
Engineered TCRs are comprehensively profiled for specificity and potential off-target effects.

Main Results:

Synthetic TCRs targeting a tumor-associated self-antigen were successfully engineered using T-Switch.
The safety and efficacy of the engineered TCRs were validated in vitro.
Extensive screening against the human proteome revealed no detectable off-target recognition.

Conclusions:

T-Switch is an effective platform for generating highly specific synthetic TCRs against self-antigens.
This approach offers a viable strategy to bypass T-cell tolerance for developing novel cancer immunotherapies.
The engineered TCRs hold promise for creating next-generation T-cell-based therapeutics with improved safety and efficacy.