TCR-Vβ Usage in the Thymus and Blood of Myasthenia Gravis Patients

Abstract

In myasthenia gravis (MG) the muscle acetylcholine receptor (AChR) is the target of an autoimmune response. The anti-AChR response may originate in the thymus, which is abnormal in most MG patients and contains anti-AChR T and B cells. Microbial superantigens (sAg) may trigger autoimmune responses and in this study we sought clues as to whether sAg play a role in the pathogenesis of MG. We investigated the frequency of use of the different TCR Vβ families by the thymus and blood T cells in MG patients and in control subjects, using a multi-primer PCR assay. Identical TCR-Vβ usage was found in the thymi of MG patients and controls, except Vβ2, which showed a small increase in MG patients’ thymi. Blood T cells of MG patients used Vβ4, Vβ6, Vβ15, Vβ16 and Vβ24 significantly more than those of the controls. Vβ4 and Vβ6 are the gene families most frequently used by anti-AChR CD4+cells in MG patients. Blood T cells from MG patients used Vβ12, Vβ14, Vβ17 and Vβ18 significantly less than controls. MG patients used Vβ4 and Vβ6 significantly more in the blood than in the thymus, while the opposite occurred for Vβ7, Vβ12 and Vβ14. Controls used Vβ17 more and Vβ24 less in the blood than in the thymus. The preferential expansion of Vβ4 and Vβ6 in MG patients might reflect the immunodominance of certain AChR epitopes, or the action of a sAg outside the thymus. The minimal differences in the TCR-Vβ usage in the blood and thymus of control subjects might be due to expansion of T cell clones specific for common antigens. Identical Vβ usage in the thymi of MG patients and controls does not support an important role of the thymus as the location of anti-AChR sensitization when MG is clinically evident. The differences observed in the Vβ usage in blood and thymi of MG patients are likely to be due to preferential Vβ usage by the anti-AChR T cells in the blood.