Pattern formation and ecological feedback in antigen-immunity co-evolution

Immune systems manifest self-tolerance and respond to foreign invaders. Despite our knowledge of the molecular mechanisms involved in immune response and tolerance, an intuitive understanding of the immune-antigen relationship that determines the overall efficacy of immune control is lacking. We suggest that both features of natural immunity can be described by immune-antigen co-evolution. Extending ecological insights, we consider predator-prey interactions between immune cells and foreign or self antigen that can reach a dynamic balance through mutual adaptation. We present a minimal model of the co-evolutionary dynamics as a pair of reaction-diffusion processes in a phenotypic shape space, coupled by reciprocal interactions with finite cross-reactivity. We find that asymmetry in cross-reactivity can lead to pattern formation, indicating the emergence of antigen niches. We show in a phase diagram the regimes of balance breaking caused by pattern-forming instability: antigen extinction occurs as a result of co-localized population densities, whereas antigen escape follows the formation of alternating patterns under immune homeostasis. Thus, it is important to consider the feedback between population dynamics and pattern formation in understanding immune function and abnormality.