Résumé :
|
Communication n° 511 Natural anti-T cell receptor (TCR) antibodies are present in the serum of all individuals, with levels increasing in physiological and pathological situations such as aging, pregnancy, transplantation, retroviral infection, and autoimmune diseases. Using TCR peptides in a sensitive ELISA test, we showed that, prior vaccination against TCR determinants, HLA-DR3 patients with myasthenia gravis (MG) present increased anti-TCR antibodies directed to the dominant TCR (Vbeta5.1) used by pathogenic T cells. This was further confirmed in the experimental model of myasthenia gravis (EAMG), where Lewis rats develop an anti-Vbeta response against the dominant TCR in parallel to development of the anti-AChR response. These results suggest that a dynamic and protective regulatory network may be fashioned to target the excess of pathogenic T cells, but may not be sufficient to stop a chronic exacerbated autoimmune process. In EAMG, T cell vaccination boosted the anti-TCR response, which is accompanied with improvement of the disease. Our current studies are investigating the possibility to use TCR peptides in EAMG, opening prospects for a vaccine in patients. Moreover we investigated how widespread are these spontaneous anti-TCR antibodies in controlling responses to non-self antigens. Anti-TCR antibodies against the dominant TCR used the immune response to the model antigen HEL were generated spontaneously, with some indications of their immunomodulatory effects, terminating the immune response, thereby contributing to T-cell homeostasis. Together these data suggest that anti-TCR antibodies might participate in a physiological adaptive mechanism of autoimmunity against the TCR that could be boosted with TCR vaccine.
|