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Increased TCR avidity after T cell activation: a mechanism for sensing low-density antigen
T M Fahmy1, J G Bieler, M Edidin
1Department of Pathology and Medicine, Division of Immunopathology, Johns Hopkins University, Baltimore, MD 21218, USA. tarekf2000@yahoo.com
Immunity
|March 10, 2001
Summary
Activated T cells exhibit significantly higher T cell receptor (TCR) avidity for peptide-MHC complexes compared to naive T cells. This enhanced avidity, crucial for immune response, is linked to TCR reorganization and membrane changes.
Area of Science:
- Immunology
- Biophysics
- Cell Biology
Background:
- Activated T cells demonstrate heightened responses to antigen stimulation.
- The biophysical mechanisms underlying this increased sensitivity in activated T cells are not well understood.
Purpose of the Study:
- To investigate the biophysical basis for the enhanced sensitivity of activated T cells.
- To quantify the difference in T cell receptor (TCR) avidity between naive and activated T cells.
Main Methods:
- Quantification of TCR avidity for peptide-MHC complexes on naive and activated T cells.
- Analysis of TCR reorganization and T cell membrane cholesterol content.
- Investigation of TCR cross-linking in activated T cells.
Main Results:
- TCR avidity for peptide-MHC complexes is 20- to 50-fold higher on activated T cells compared to naive T cells.
- This increased avidity is dependent on TCR reorganization and T cell membrane cholesterol levels.
- Enhanced avidity is attributed to increased TCR cross-linking on activated T cells.
Conclusions:
- Activation-induced membrane (AIM) changes in TCR avidity represent a novel mechanism for heightened T cell sensitivity.
- This mechanism enhances the ability of activated T cells to detect low antigen concentrations in peripheral tissues.