The adaptive immune system – a subsystem of the overall immune system – comprises specialized cells and processes that eliminate or prevent pathogen growth by using the experience of past infections to prepare its limited repertoire of specialized receptors to protect organisms from future threats. Recently, scientists at CNRS and Ecole Normale Superieure, Paris and the University of Pennsylvania developed a general theoretical framework from first principles that allowed them to predict the composition of receptor repertoires optimally adapted to minimize the biological cost of infections from a given pathogenic environment. Their theory predicts that the immune system will have more receptors for rare antigens; individuals exposed to the same infections will have largely different repertoires; and competitive antigen/receptor binding and selective amplification of stimulated receptors are key to creating optimal repertoires. Their findings explain how limited populations of immune receptors can self-organize to provide effective immunity against highly diverse pathogens, and moreover inform the design and interpretation of experiments surveying immune repertoires.
Researchers Thierry Mora and Aleksandra M. Walczak discussed the paper that they and their colleagues published in Proceedings of the National Academy of Sciences. “A great deal of very interesting theoretical work has been done on the problem of avoiding autoimmunity – that is, recognizing self-proteins – essentially viewing the immune system as a device for discrimination,” Mora tells Medical Xpress. “We wanted to study the problem from a different perspective: As, in essence, introduced by Sir Frank Macfarlane Burnet’s theory of clonal selection1, an adaptive immune system adapts to its pathogenic or antigenic environment. We wanted to see how far we could take the idea that the composition and diversity of the immune repertoire reflects that of the environment – in other words, the repertoire is an internal representation of its environment – aimed at minimizing the cost of infections to the tissues of the organism.” In short, Mora says, this is one way to look at the complicated problem of the structure of immune repertoires.
This approach allowed the scientists to create a new framework that makes it unnecessary to explicitly model intracellular communication, cell differentiation, activation of cofactors, coordination of different cell types, the interaction with the innate immune system, and the full complexity of the recognition process. “Our goal was to make concrete predictions about adaptive immune repertoires that are general and not specific to one kind of cell type in specific conditions. While these features all play an important role in the functioning of real immune systems, we wanted to see what the essence was, what an optimal but simplified immune system would look like,” Walczak points out. “We didn’t want to concentrate on the fine details of repertoires, but rather took a step back and try to see what we could learn from global properties while still being realistic enough to make concrete statements about real immune systems – for example, the fact that two individuals in similar environments can have very different optimal immune repertoires.” The scientists discovered that their assumption – that is, the system needs to minimize the cost of infection given a limited number of encounters – actually structures the repertoire.