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Molecular recognition in health and disease

The adaptive and the innate immune system are essentially based on a highly specific and efficient interaction with antigens of all kinds. The molecular basis of this interaction however in many cases remains enigmatic. Antigenic architecture, steric requirements, epitope structure and affinity vs avidity severely affect individual interaction profiles.

Therefore we focus on analyses of molecular and structural aspects of the interaction, with respect to the epitopes on the surface of the antigens as well as the paratopes of the antibodies or other interacting partners. Thereby a simultaneous use of combinatorics for isolation of antibodies and peptidic ligands and techniques for identification and analyses of the interaction is essential.

One class of structures the recognition of which is highly important in many processes are carbohydrates. Carbohydrates are increasingly recognised as important players in driving and modulating immune responses. Understanding molecular principles of their recognition in health and disease offers a large potential for novel and optimised biologicals and targeting approaches.

Carbohydrates and particularly N-glycans from non-human sources differ from those present in humans and represent immunogenic structures that are perfectly recognized by the human immune system. The immunogenicity of carbohydrates is well established but the availability of high affinity binders and molecular data on mechanisms governing the interaction with antibodies are still scarce.

Such structures are synthesised in vivo by highly specific enzymes, e.g. glycosyltransferases, the availability and use of which can provide access to synthetic preparation routes.

An interesting example is the recognition of carbohydrate epitopes. This can be directed against endogenous antigens, e.g. in the blood group antigens, or exogenous, such as the alpha-Gal antigen. In the context of Th2 biased immunity, the usually lower affinity recognition by IgG can convert into an IgE-mediated recognition resulting in anaphylactic reactions against, food and biologicals.  The underlying molecular mechanisms however remain unclear.

An identification of carbohydrate-specific immunoglobulins and other molecules could provide unique insights into their recognition. Understanding principles of their immunogenicity and recognition offers a large potential for exploit or avoid the immunogenicity of biologicals.