Regulation of IL-15 secretion via the leader peptide of two IL-15 isoforms.
The secretion of IL-15, a potent modulator of T, B, and NK lymphocyte functions, is likely to be tightly controlled. Here, we show that human T lymphoblasts transcribe the IL-15 gene and generate an alternative splicing product that codes for the same amino acid composition as the mature IL-15 protein, but produces an IL-15 precursor protein with a shorter signal peptide. Both alternative splicing products are transcribed by non-IL-15-secreting lymphocytes, suggesting that IL-15 secretion is not primarily controlled at the level of transcription. We generated an in vitro system for correlating the expression, translation, and secretion of IL-15 or IL-15-IgG1 fusion protein. This revealed that the two isoforms of IL-15 or a truncated IL-15 variant, both alone and fused to human IgG1, are all transcribed and translated, but not efficiently secreted. After replacing the IL-15 leader peptide with a foreign one, translation and secretion clearly increase. These results suggest that IL-15 is mainly controlled at the level of translation and secretion.
Onu
A
A
Institute of Immunology, University Hospital Benjamin Franklin, Free University of Berlin, Germany.
Pohl
T
T
Krause
H
H
Bulfone-Paus
S
S
D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D006801:Humans; D019409:Interleukin-15 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis / Q000235:genetics; D021382:Protein Sorting Signals / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
D019409:Interleukin-15; D021382:Protein Sorting Signals; D012333:RNA, Messenger