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Assessment of the Synaptic Interface of Primary Human T Cells from Peripheral Blood and Lymphoid Tissue
Published on: July 30, 2018
Self-reactive human CD4 T cell clones form unusual immunological synapses
David A Schubert1, Susana Gordo, Joseph J Sabatino
1Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
The Journal of Experimental Medicine
|February 8, 2012
Summary
Self-reactive T cells in autoimmune diseases show impaired immunological synapse formation. These cells exhibit active signaling but fail to accumulate peptide-MHC complexes, unlike virus-specific T cells.
Area of Science:
- Immunology
- Autoimmunity
- Cellular immunology
Background:
- Recognition of self-peptide-MHC (pMHC) complexes by CD4 T cells is implicated in autoimmune disease pathogenesis.
- Understanding the dynamics of T cell interactions with self-antigens is crucial for developing targeted therapies.
Purpose of the Study:
- To analyze the formation of immunological synapses (IS) in self-reactive T cell clones from patients with multiple sclerosis and type 1 diabetes.
- To compare the IS formation and T cell receptor (TCR) binding kinetics of self-reactive T cells with virus-specific T cells.
Main Methods:
- Analysis of immunological synapse formation in self-reactive and influenza-specific T cell clones.
- Microscopy to observe peptide-MHC (pMHC) accumulation and TCR microclusters.
- 2D affinity measurements to determine TCR binding on-rate and off-rate to pMHC.
Main Results:
- Self-reactive T cells displayed active TCR signaling (phosphorylated microclusters) but limited pMHC accumulation in the IS.
- Virus-specific T cells efficiently accumulated pMHC complexes in microclusters and the central supramolecular activation cluster (cSMAC).
- Self-reactive T cells exhibited a slow TCR binding on-rate to pMHC, unlike virus-specific T cells.
Conclusions:
- Unusual IS features in self-reactive T cells may allow escape from negative selection in the thymus.
- These same features might enable effector function acquisition in peripheral tissues, contributing to autoimmune disease.
- Defective IS formation in self-reactive T cells presents a potential therapeutic target for autoimmune disorders.
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