Antibodies are shape shifters. What is shape shifting? It’s a common theme in fairytales and involves the transformation of an animal or person into something else, whether permanently or transiently. For example, a woman can become a bear or a deer, to escape a pursuer. Antibodies also shape shift, changing their characteristics in the course of an immune response, and over the course of a human lifetime, due to unknown factors. This shape shifting can have profound implications on the development of immune complexes – or anti-idiotypic antibodies, and autoimmune disease.
Why do antibodies shape shift, and what do we mean? Antibodies made in response to an attack by an intruder (flu virus, for example) can be inflammatory – where as later on, they can shift shape (probably related to glycosylation and become regulatory. In other words, unless antibodies are rigidly constrained in their synthesis (petrified, in fairytale parlance) by modification of the means of protein expression in the cell, an antibody cannot truly be construed to be a single, monomorphic product. Antibodies to a single target can be more- or less- glycosylated, and the glycosylation has a profound influence on their processing by antigen presenting cells and the impact of the Tregitopes that they contain, on immune response to their target antigen.
The shape shift has dramatic implications for the immunogenicity of monoclonals – is it possible that glycosylation preference changes as CHO cell cultures mature? The answer is yes, and that’s something that the process folks have know about for a long time. Watch this space for more on this topic.