The role of antigen-competitive dynamics in regulating the immune response

Abstract

The clonal expansion of T cells during an infection is tightly regulated to ensure an appropriate immune response against invading pathogens. Although experiments have mapped the trajectory from expansion to contraction, the interplay between mechanisms that control this response are not fully understood. Based on experimental data, we propose a model in which the dynamics of CD4+ T cell expansion is controlled through the interactions between T cells and antigen-presenting cells, where T cell stimulation is proportional to antigen availability and antigen availability is regulated through downregulation of antigen by T cells. This antigen-dependent-feedback mechanism operates alongside an intrinsic reduction in cell proliferation rate that may also be responsible for slowing expansion. Our model can successfully predict T cell recruitment rates into division, expansion and clonal burst size per cell when initial precursors are varied or when T cells are introduced late into an ongoing immune response. Importantly, the findings demonstrate that a feedback mechanism between T cells and antigen presenting cells, along with a reduction in cell proliferation rate, can explain the ability of the immune system to adapt its response to variations in initial conditions or changes that occur later in the response, ensuring a robust yet controlled line of defence against pathogens.