Immunoregulation by Vbeta specific antibodies in myasthenia gravis: mining physiological T cell homeostasis for TCR...

Besides regulatory T cells, also comprising T cell receptor (CR)-specific T cells, it is increasingly evident that natural autoantibodies, among which anti-TCR antibodies represent additional immunomodulators in the immune system. We took advantage of myasthenia gravis (MG), a well-characterized antibody-mediated autoimmune disease, to demonstrate that without prior vaccination against TCR determinants, patients with MG present increased circulating anti-TCR antibodies directed to the dominant TCR used by pathogenic T cells. These findings, pointing to a regulatory protective role of anti-TCR antibodies, are discussed in the context of the mechanisms of action and the physiological role of anti-TCR antibodies in T cell homeostasis, and of the puzzling world of regulatory T cells. Natural anti-TCR antibodies are found in the serum of all individuals, with prevalence in physiological and pathological situations such as ageing, pregnancy, allograft transplantation, retroviral infection, and autoimmune diseases, including MG. The common link is the mounting of immune responses against alloantigens, pathogens or autoantigens, conferring on anti-TCR antibodies a broader role in controlling responses to any antigen (self or non-self) and more generally in T cell homeostasis. This homeostasis mechanism may well be exploited in therapeutic strategies based on TCR peptide vaccination in autoimmune diseases.