Epitope mapping of autoantigens using recombinant proteins and synthetic peptides

In order to evaluate mechanisms of autoantibody production, three hypotheses (random polyclonal B cell activation, molecular mimicry and immune response against restricted self antigens) were considered in relation to autoantibody recognition. Polyclonal B cell activation was considered unlikely because lupus sera recognized a relatively small number of eukaryotic protein antigens on immunoblots and failed to show enhanced reactivity against prokaryotic epitopes. Although two interesting examples of molecular mimicry between autoantigens and two different viruses have been suggested, it is yet to be shown that lupus antibodies bind to the shared epitopes on the viruses and that the viruses induce such antibodies. Finally, epitope mapping of several different autoantigens suggest that the antigens are themselves the focus of the immune response and initiate and/or maintain autoantibody production.