Altered interleukin-2 receptor α-chain is expressed in human T-cell leukaemia virus type-I-infected T-cell lines and human peripheral blood mononuclear cells of adult T-cell leukaemia patients through an alternative splicing mechanism.

A polymerase chain reaction (PCR) method was used to detect the interleukin-2 receptor α-chain (IL-2Rα) chain which lacks the conventional transmembrane (TM) domain in mRNA from human T-cell leukaemia virus type-I (HTLV-I) -infected cell lines or peripheral blood mononuclear cells (PBMC) isolated from adult T-cell leukaemia (ATL) patients. Primer pairs encompassing the TM domain were selected to generate a 357-base pair (bp) fragment. A 146-bp PCR product was observed consistently in addition to the target 357-bp PCR product in mRNA from HTLVI-infected cell lines, such as MT-1, MT-2, MT-4 and in PBMC isolated from ATL patients. However, this 146-bp PCR product was undetectable in HTLV-1-negative cell lines. The product wan also detected in PBMC from normal individuals if activated in vitro with phytohaemagglutinin but not without stimulation. DNA sequence analyses revealed that exons from 5 to 7, which define a 211-bp region containing the conventional TM domain, were deleted in the 146-bp PCR product. The C-terminal amino acid sequence starting from Gly¹⁷⁴ of the 211-bp-deleted molecule was distinct from that of conventional IL-2Rα as a result of an altered reading frame. We identified a 45 000 MW peptide generated from IL-2Rα mRNA through this exon skip in cell lysate of MT-1 and MT-2 by Western blot analyses using an antibody raised against the peptides specific to an altered IL-2Rα. Our results indicate that an altered IL-2Rα chain is expressed in HTLV-1-infected T lymphocytic cell lines and in ATL patients. [ABSTRACT FROM AUTHOR]