Characterization of alternative splice variants of human interleukin-2

We used reverse transcription-PCR to analyse IL-2 mRNA transcripts obtained from activated human peripheral blood mononuclear cells of healthy donors. We have identified and characterized two alternatively spliced mRNAs, called IL-262 and PL-283. As shown by DNA sequence analysis, IL-2S2 and IL-283 lack exon 2 or exon 3, respectively. To test functions of IL-282 and FL-263, we expressed IL282, IL-283, and wild type IL-2 in GS115 PicHa pastoris expression system. Recombinant proteins were identified by SDS-PAGE and Western blot analysis with anti-IL-2 antibody. Each recombinant protein had the expected molecular weight. We tested whether IL-2, IL-282 and IL-283 proteins have different functions. In contrast to IL-2, IL-282 and IL-283 had no costimulatory effect on T-cell proliferation. Preliminary data show that IL-282 and IL-283 inhibit FL-2-induced T cell proliferation in vitro. This inhibition is not mediated through toxicity. We hypothesize that IL-282 and IL-283 are competitive inhibitors of IL-2 binding to IL-2 receptors. Additional studies are in progress to test this hypothesis.