Influence of cross immunoreactive network topology and internal dynamics of the immune system on antigenic cooperation

The recent discovery of antigenic cooperation (AC) provides an explanation for the persistence of viral strains in the host during chronic infection (like in hepatitis C virus) that better fits the experimental evidence when compared to the immune-escape hypothesis. As it is currently understood, AC leverages altruistic strains of the virus that sacrifice their own fitness through immunodominance to benefit persistent strains. This dynamic leaves sections of the cross immunoreactivity network (CRN) invisible to the host’s immune system, with persistent strains located in such invisible sections, a phenomenon known as local immunodeficiency (LI). However, all the efforts so far have focused on the interacting dynamics of the viral strains with the entire immune response accounted as a whole. It remains unclear whether the LI emerges solely from the topology of the CRN or if the intricate inner functioning of the immune system has a significant contribution. We investigate these inquiries on LI by fine-graining the immune system dynamics and by exploring the influence of network topology on AC. Our modeling approach is broadly applicable to understanding the internal dependencies of cooperation on internal dynamics of distinct immune features, along with their role in autoimmune and chronic disease