T-cell receptor gene rearrangement in T-cell large granular leukocyte leukemia: Preferential Vα but diverse Jα usage in one of five patients

T-γ lymphoproliferative disease (T-γ LPD) is a chronic disorder of mature T cells that is associated with neutropenia and autoimmune phenomena. Although the progression of the lymphoproliferation is indolent, it is often associated with a monoclonal proliferation of T-cell-type large granular lymphocytes (LGL) that manifest multiple in vitro suppressor and cytotoxic activities. We considered the possibility that the granulocytopenia or anemia might represent an autoimmune disorder mediated by the monoclonal LGL via T- cell receptor (TCR) recognition of an antigen involved in hematopoiesis. Therefore, in an effort to characterize the usage of the TCR α- and β- chain genes in patients with T-γ LPD, we cloned and sequenced TCR α- and β-chain mRNAs derived from the T-cell type LGL of five patients. The five patients studied did not use a common Vα nor a common Jα segment. However, an unusual finding was observed in one of the patients where the occurrence of a single variable-diversity-junctional (VDJ) rearrangement of the β chain confirmed the monoclonal origin of the LGL proliferation. In accord with this evidence for monoclonality, many of the cells studied used a common Vα (Vα19.1). In contrast to this common Vα usage, there was a marked diversity of the Jα segments and N-region addition that were associated with the Vα19.1 segment. This pattern of common Vα usage associated with different N and Jα segments suggests an immune-mediated selection process affecting the TCR α chain occurring after the transformation event that established the clone. We suggest that the T-cell-type LGL malignant clone might have developed autoreactivity conferred by the selected TCR α chain and that this autoreactivity might be implicated in this patient's anemia.