Naturally occurring antibodies, many of them preformed IgM, are vanguards of humoral immune defense. Hence, in chronic immune complex diseases, IgM do play a minor role the major part being taken over by IgG with their four subclasses IgG1, IgG2, IgG3 & IgG4. In this network, the epitope specificity is not the only criterion, but also the way it is presented to the antigen-recognizing apparatus: the surrounding of the epitope.
Antibodies can be generated in vitro by panning gene libraries with phage display. The Structural Genomics Consortium (www.thesgc.org) http://www.thesgc.org provides patient-based renevable antibodies. Streamlined methods for high throughput antibody generation similar to an ‘Antibody Factory’ may minimise effort and provide a robust source for antibodies.
Thanks to nanontechnology and to crystallography and proteomics the conviction grows, that it is the fine structure of the partners (not only amino acid sequence but also 3D-configuration, carbohydrate substitution, isoelectric points) which decides on ultimate properties of immune complexes conveyed by the complementarity determining regions (CDR) on the Fab recognition site of the Ig molecule. The vitreous water electron cryomicroscopy provides further insights (Nobel Prize in Chemistry 2017, University of Lausanne, Switzerland, through the work of Jacques Dubochet).
Influence of some amino acids, like tyrosin, might prevail. Immune complexes are a normal phenomenon serving to remove antigen – however, if they last and remain detectable in peripheral blood or in tissues, they express underlying pathology. Their impact on components of innate immunity is as yet ill known.