Computational investigations into the origins of short-term biochemical memory in T cell activation.
Recent studies have reported that T cells can integrate signals between interrupted encounters with Antigen Presenting Cells (APCs) in such a way that the process of signal integration exhibits a form of memory. Here, we carry out a computational study using a simple mathematical model of T cell activation to investigate the ramifications of interrupted T cell-APC contacts on signal integration. We consider several mechanisms of how signal integration at these time scales may be achieved and conclude that feedback control of immediate early gene products (IEGs) appears to be a highly plausible mechanism that allows for effective signal integration and cytokine production from multiple exposures to APCs. Analysis of these computer simulations provides an experimental roadmap involving several testable predictions.
Locasale
Jason W
JW
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America. Locasale@MIT.edu
D056704:Adaptive Immunity; D000938:Antigen-Presenting Cells / Q000276:immunology; D005246:Feedback; D017781:Genes, Immediate-Early; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D016014:Linear Models; D008285:Major Histocompatibility Complex; D008570:Memory, Short-Term; D009010:Monte Carlo Method; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma