Natural splicing of exon 2 of human interleukin-15 receptor alpha-chain mRNA results in a shortened form with a distinct pattern of expression

We report the existence of eight different interleukin-15 receptor alpha-ch ain (IL-15R alpha) transcripts resulting from exon-splicing mechanisms with in the IL-15R alpha gene. Two main classes of transcripts can be distinguis hed that do or do not (Delta 2 isoforms) contain the exon 2-coding sequence . Both classes were expressed in numerous cell lines and tissues (including peripheral blood lymphocytes) art comparable levels and could be transcrib ed in COS-7 cells, and the proteins were expressed at the cell surface. Bot h receptor forms displayed numerous glycosylation stales, reflecting differ ential usage of a single N-glycosylation site as well as extensive O-glycos ylations. Whereas IL-15R alpha bound IL-15 with high affinity, Delta 2IL-15 R alpha was unable to bind IL-15, thus revealing the indispensable role of the exon 2-encoded domain in cytokine binding. A large proportion of IL-15R alpha was expressed at the nuclear membrane with some intranuclear localiz ation, supporting a potential direct action of the IL-15 IL-15R alpha compl ex at the nuclear level. In sharp contrast, Delta 2IL-15R alpha was found o nly in the non-nuclear membrane compartments, indicating that the exon alph a-encoded domain (which is shown to contain a potential nuclear localizatio n signal) plays an important role in receptor post-translational routing. T ogether, our data indicate that exon 2 splicing of human IL-15R alpha is a natural process that might play regulatory roles at different levels.