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A T cell clone's avidity is a function of its activation state
M D Hesse1, A Y Karulin, B O Boehm
1Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|July 24, 2001
Summary
T cell responsiveness to antigen (Ag) dose depends on signal strength, not just T cell receptor (TCR) affinity. Functional avidity changes with T cell history, impacting autoimmune disease understanding.
Area of Science:
- Immunology
- Computational Biology
- Systems Biology
Background:
- The relationship between antigen (Ag) dose, T cell receptor (TCR) affinity, and T cell function remains unclear.
- How signal strength affects the kinetics of cytokine production by individual T cells is not well understood.
Purpose of the Study:
- To investigate how Ag dose-dependent T cell functions, like cytokine production, reflect TCR affinity.
- To determine how signal strength influences the kinetics of cytokine production in individual T cells.
Main Methods:
- Utilized a computer-assisted ELISPOT approach to monitor IFN-gamma release from CD4 T cells.
- Titrated nominal peptide antigen presented by antigen-presenting cells (APCs).
Main Results:
- Cytokine production frequency, per-cell output, and production onset were functions of signal strength.
- Individual T cell activation thresholds followed a Gaussian distribution, while population-level responses were sigmoidal.
- T cell clone dose-response curves showed cyclic shifts toward lower Ag concentrations over time since last Ag encounter.
Conclusions:
- T cell functional avidity is not constant but depends on the T cell's history of Ag exposure.
- Shifting activation thresholds have implications for understanding and potentially treating autoimmune diseases.