Overexpression of Select T Cell Receptor Vβ Gene Families within CD4+ and CD8+ T Cell Subsets of Myasthenia Gravis Patients: A Role for Superantigen(s)?

The principal symptoms of myasthenia gravis (MG), muscle weakness and fatigue due to impaired neuromuscular transmission, are caused by autoantibodies to the muscle nicotinic acetylcholine receptor (AChR). The mechanisms underlying the autoimmune response, however, appear to be initiated by activation of specific HLA class II–restricted CD4+ T lymphocytes. Thus, central to elucidating the causation of MG is determining how T cells are recruited to contribute to misguided immunological assaults on the major autoantigenic target, AChR. By combining a polymerase chain reaction (PCR)–based strategy and Southern blot technique, we have analyzed the frequency of expression of 22 individual T cell receptor (TCR) Vβ gene subfamilies in CD4+ and CD8+ peripheral blood T cell subsets derived from eight MG patients and seven healthy controls. The quantification of relative usage of individual TCR Jβ gene segments was performed by hybridization of PCR-amplified products (specifically Vβ1-Cβ) with a complete panel of 32P-5′-end-labeled Jβ-specific oligonucleotide probes, followed by scanning analysis of autoradiographs. Comparisons of data obtained from Vβ analyses of T cells from MG patients with those from healthy individuals established that MG patients significantly overexpressed Vβ1, Vβ13.2, Vβ17, and Vβ20 gene family members within both CD4+ and CD8+ T cell sub-populations. Moreover, analysis of the relative utilization of individual TCR Jβ gene segments in Vβ1+/CD4+ and Vβ1+/CD8+ T lymphocytes revealed distribution patterns in patients indistinguishable from those recorded in the corresponding cell subsets derived from controls. T lymphocytes from MG patients displayed a biased overexpression of four TCR Vβ gene segments: Vβ1, Vβ13.2, Vβ17, and Vβ20. The relative frequencies of association of individual Vβ1 (Dβ)Jβ combinations revealed that Jβ gene usage in the Vβ1-overrepresented T cell subsets had normal distribution patterns. It can thus be deduced that Jβ gene segment products appear not to have a selective effect on the process leading to overexpression of Vβ1 exons in MG patients. Hence, our observations suggest a possible role for superantigen(s) in the T cell activation in MG patients.