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The Journal of Immunology, Vol 158, Issue 1 255-262, Copyright © 1997 by American Association of Immunologists

ARTICLES

Regulation of IL-15 secretion via the leader peptide of two IL-15 isoforms

A Onu, T Pohl, H Krause and S Bulfone-Paus
Institute of Immunology, University Hospital Benjamin Franklin, Free University of Berlin, Germany.

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.


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