TCR-V beta usage in the thymus and blood of myasthenia gravis patients

In myasthenia gravis (MG) the muscle acetylcholine receptor (AChR) is the t arget of an autoimmune response. The anti-AChR response may originate in th e thymus, which is abnormal in most MG patients and contains anti-AChR T an d B cells. Microbial superantigens (sAg) may trigger autoimmune responses a nd in this study we sought clues as to whether sAg play a role in the patho genesis of MG. We investigated the frequency of use of the different TCR V beta families by the thymus and blood T cells in MG patients and in control subjects, using a multi-primer PCR assay. Identical TCR-V beta usage was f ound in the thymi of MG patients and controls, except V beta 2, which showe d a small increase in MG patients' thymi. Blood T cells of MG patients used V beta 4, V beta 6, V beta 15; V beta 16 and V beta 24 significantly more than those of the controls. V beta 4 and V beta 6 are the gene families mos t frequently used by anti-AChR CD4(+) cells in MG patients. Blood T cells f rom MG patients used V beta 12, V beta 14, V beta 17 and V beta 18 signific antly less than controls. MG patients used V beta 4 and V beta 6 significan tly more in the blood than in the thymus, while the opposite occurred for V beta 7, V beta 21 and V beta 14. Controls used V beta 17 more and V beta 2 4 less in the blood than in the thymus. The preferential expansion of V bet a 4 and V beta 6 in MG patients might reflect the immunodominance of certai n AChR epitopes, or the action of a sAg outside the thymus. The minimal dif ferences in the TCR-V beta usage in the blood and thymus of control subject s might be due to expansion of T cell clones specific for common antigens. Identical V beta usage in the thymi of MG patients and controls does not su pport an important role of the thymus as the location of anti-AChR sensitiz ation when MG is clinically evident. The differences observed in the V beta usage in blood and thymi of MG patients are likely to be due to preferenti al V beta usage by the anti-AChR T cells in the blood. (C) 1998 Academic Pr ess.