Molecular biology and immunology for clinicians 25: defense collagens

The adaptive immune response specializes in reacting efficiently and rapidly with protein antigens. Many pathogens and host cells are coated with carbohydrates (more about lipid antigens and the response thereto in a future installment of this series). The carbohydrate arrays on pathogens are remarkable for their relative lack of diversity, remarkable conservation, and how different they are from the carbohydrates found on mammalian cells. Thus, they represent excellent targets for the innate immune response, which is characterized by limited effector molecule heterogeneity. Defense collagens are a class of innate immune response recognition proteins targeting these common carbohydrate motifs, a class you may not have encountered previously. These invariant germ-line encoded proteins are not produced as a specific response to a particular antigen. Nonetheless, they too have an antigen-binding site, called the carbohydrate recognition domain with the other end of the molecule (made up of collagen-like domains) devoted to the transmission of biologically relevant information, analogous with the antibody molecule's Fc component, but this is where the similarities end. Defense collagens have been broadly viewed as an "anti-antibody," broadly similar in structure and function. Despite the fact that they are germline-encoded and do not have individual antigen specificity, their phylogenetic longevity and durability prove the value of defense collagens in maintaining the host. On the basis of emerging studies, they may play important roles in the defense against many pathogens and in the pathogenesis of rheumatologic and other diseases. Thus, they are good targets for studies to better understand our diseases and to craft therapeutic manipulations in the future.