Adaptive discrimination between harmful and harmless antigens in the immune system by predictive coding

The immune system discriminates between harmful and harmless antigens based on past experiences; however, the underlying mechanism is largely unknown. From the viewpoint of machine learning, the learning system predicts the observation and updates the prediction based on prediction error, a process known as “predictive coding.” Here, we modeled the population dynamics of T cells by adopting the concept of predictive coding; conventional and regulatory T cells predict the antigen concentration and excessive immune response, respectively. Their prediction error signals, possibly via cytokines, induce their differentiation to memory T cells. Through numerical simulations, we found that the immune system identifies antigen risks depending on the concentration and input rapidness of the antigen. Further, our model reproduced history-dependent discrimination, as in allergy onset and subsequent therapy. Taken together, this study provided a novel framework to improve our understanding of how the immune system adaptively learns the risks of diverse antigens.