Biomarkers, self-antigens and the immunological homunculus

Abstract

The notion of the immunological homunculus arose from the observations (1) that the healthy adaptive immune system is inclined to respond (T cell reactivity and autoantibodies) to particular sets of body molecules (self-antigens) and (2) that autoimmune diseases are characterized by sets of autoimmune reactivity to some of the very same self-antigens recognized by healthy subjects - with an obvious difference in outcome. I termed this natural autoimmune structuring of the immune system, the immunological homunculus - the immune system's representation of the body. What might be the selective advantage of an immune system expressing patterns of built-in autoimmunity to particular sets of self-molecules? To better characterize the homunculus, we have used informatic tools to study patterns of antibodies to many hundreds of self-molecules arrayed on glass slides - an antigen chip of our design. Results using the antigen chip suggest that the particular self-reactivities comprising the homunculus could serve as a set of biomarkers that help the immune system initiate and regulate the inflammatory processes that maintain the body.