MALIGNANT AND NORMAL T-CELLS SHOW RANDOM USE OF T-CELL RECEPTOR-ALPHACHAIN VARIABLE REGIONS IN PATIENTS WITH CUTANEOUS T-CELL LYMPHOMA

Cutaneous T-cell lymphoma (CTCL) is a malignancy of mature T lymphocyt es, most of which express alpha/beta type T-cell receptors (TCRs). The cause of CTCL is unknown, but hypotheses postulating chronic stimulat ion of TCRs by superantigen or by a leukemogenic virus have been propo sed. Either mechanism might produce bias in the TCR variable (V) regio n types used by the malignant cells. To determine if TCR alpha use is restricted in CTCL, we used reverse transcription and the polymerase c hain reaction to determine V alpha and V beta usage by malignant cells purified from the peripheral blood of leukemic patients with CTCL. Us age of alpha chain V region segments appeared totally random; malignan t lymphocytes isolated from each of six patients used different V alph a regions. As has been previously reported, no bias was found in beta chain V region usage either. In addition to productive (in frame) TCR V region mRNAs in malignant cells from each patient, we detected non-p roductive (out of frame) beta chain transcripts in these cells in two of six patients, and non-productive alpha chain transcripts in five of six. Residual normal peripheral blood lymphocytes from these patients showed a random, polyclonal or oligoclonal pattern of V region usage. We conclude that there is no bias in V region usage in CTCL, making i t unlikely that interactions between superantigen or virus and the TCR V regions play a role in the pathogenesis of CTCL.