CD3(-CELL RECEPTOR V-BETA GENES() LEUKEMIC LARGE GRANULAR LYMPHOCYTESUTILIZE DIVERSE T)

CD3(+) large granular lymphocyte (LGL) leukemia is a disease of unknow n etiology characterized by clonal proliferation of T cells that usual ly express T-cell receptor (TCR) alpha beta heterodimers. The purpose of this study was to identify the variable (V), joining (J), and diver sity (D) region TCR beta-chain genes expressed by CD3(+) LGL leukemic cells in an attempt to gain insights into the etiology of this disorde r. Twelve patients with LGL leukemia were studied, including seven wit h both LGL leukemia and rheumatoid arthritis (RA). RA is also a diseas e of unknown etiology that occurs frequently in patients with LGL leuk emia. Clonally expanded T cells that express specific TCR V beta genes have been identified in fluid and tissue specimens from the joints of patients with RA. In this study, V beta expression was determined by PCR using a panel of 22 unique V beta primers to amplify cDNA prepared from peripheral blood mononuclear cells (PBMC). A dominant V beta gen e product was readily apparent in all patients. To confirm that the do minant V beta gene originated from a clonal expansion, DNA fragments c orresponding to the dominant V beta genes were subcloned into plasmids and independently isolated recombinants were sequenced. V-D-J region sequences that occurred repeatedly indicated clonality. The V beta and J beta genes expressed by the leukemic cells showed a pattern of dist ribution that followed the frequency with which these genes are repres ented in the peripheral blood. The residues corresponding to the third complementarity-determining region of the TCR beta chain were differe nt in all cases. A specific pattern of VDJ usage was not identified fo r those patients with both LGL leukemia and RA; however, utilization o f V beta-6 by LGL clones (N = 3) was observed only in the setting of R A. These data suggest that leukemic CD3(+) LGL cells have been clonall y transformed in a random fashion with respect to the TCR beta chain.