Rebuilding immunoreceptors reveals their mode of activation


Just 110 years ago in 1900, Paul Ehrlich, one of the founding fathers of modern immunology, gave the Croonian Lecture to the Royal Society in London “On Immunity with Special Reference to Cell Life”. In this lecture he explained his “side-chain theory” proposing for the first time a receptor-ligand interaction as the basis for the immune reaction against bacterial toxins. This theory fell in discredit when it was found that our immune system does not only react against toxins but against a diverse universe of different molecular structures that are foreign to our body. Since then, immunologists have made many important discoveries better describing the cells and molecules of our immune system. It is now known that B lymphocytes are the cells that produce antibodies once they are activated by the binding of a foreign molecule (called antigen) to the antigen receptor. Antigens can be a virus, a bacterial molecule or any higher-structured molecule foreign to our body. Other receptors on the cell surface are only activated when they bind to a specific ligand molecule that brings the receptor into the proper conformation required for signalling. How then can the B cell antigen receptor (BCR) achieve this by binding to thousands of different structures?


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