Dynamic regulation of T cell activation by coupled feedforward loops

Abstract: The adaptive immune system responds to foreign invaders by activating T cells. However, this response is perilous if T cells are activated by the wrong signal or if they remain activated unduly long after the threat has been eliminated. It is therefore important that T cells get activated only by the right kind of signals and for the right duration. The dominant theory in immunology over recent decades has been that a T cell must receive at least two signals before it can become activated. It is, however, unclear whether and how this two-signal requirement ensures that T cell activation is provoked only by the right signals and that the response is just long enough. Here, we propose that the two signal requirement induces a novel coherent feedforward motif whose properties align with those preferred for an ideal immune response. Further consideration of the interaction between helper and regulatory T cells induces a composite feedforward-feedback motif, analysis of which generates a condition for a healthy concentration of activated T helper cells.