Progress in the research of cellular and humoral immunity has been exponential during the past decade, although it is still insufficient to explain fully the pathogenesis of autoimmunity. Over the same period, an understanding of the cytokine network and the extracellular proteolysis cascades has grown considerably. Here, Ghislain Opdenakker and Jo Van Damme propose the REGA-model (Remnant Epitope Generates Autoimmunity) to explain the generation of autoantigens and their interaction with the T-cell receptor complex. Although this model may be applied to all known autoimmune diseases, multiple sclerosis has been used as the specific example here.