Abnormal T-cell expansion and V-gene usage in myasthenia gravis patients

To determine the extent of V-gene heterogeneity of blood T lymphocytes in patients suffering from Myasthenia Gravis (MG), we used eight recently available monoclonal antibodies (MoAb), directed against different V alpha and V beta gene products of the variable part of the T-cell receptor (TCR), covering approximately 25% of the alpha/beta T cells in normal peripheral blood (PBL) of healthy individuals. Using a two-colour immunofluorescence method, we could calculate the expression of alpha/beta V segments within the two major T-cell subsets, CD4-/CD8+ and CD4+/CD8- lymphocytes. Twenty-seven per cent (4/15) of the MG patients had T cells showing signs of abnormal expansion. Furthermore, among these expanded T cells, a restricted V beta 12 gene expansion could be seen, in three out of four patients. No correlation between TCR V-gene usage and HLA haplotypes (HLA-A, -B, -DR and -DQ) could be seen. Our data suggest that the majority of MG patients have abnormally expanded T-cell clones. The relevance of these findings is discussed.