Modelling the impact of antigen kinetics on T-cell activation and response.

Cytotoxic T lymphocyte (CTL) responses are thought to be important for the control of many viral and other infections. Qualitative aspects of the CTL response, including the epitope specificity, affinity, and clonal composition, may affect the ability of T cells to mediate infection control. Although it is clear that the mode of introduction and the dose of antigen can affect these qualitative aspects of the response, little is understood of the mechanisms. We have developed an in silico model of the CTL response, which we use to study the impact of antigen dose, antigen kinetics and repeated antigen delivery on the response. The results suggest that recent observations on differences in response to killed antigen can be explained simply by differences in timing of T-cell activation. These findings may provide insight into how different vaccination strategies can quantitatively and qualitatively affect the outcome of the immune response.