MOLECULAR-CLONING, SEQUENCE, EXPRESSION, AND PROCESSING OF THE INTERLEUKIN-16 PRECURSOR

Interleukin 16 (IL-16) has been shown to function as chemoattractant f actor, as a modulator of T-cell activation, and as an inhibitor of imm unodeficiency virus replication, The recent identification of inconsis tencies in published IL-16 cDNA nucleotide sequences led to the propos al that IL-16 is synthesized in the form of a large precursor protein (pro-IL-16). To identify the true transcriptional start of the IL-16 m RNA rapid amplification of cDNA ends methods were applied. The complet e pro-IL-16 cDNA was subsequently molecularly cloned, sequenced, and e xpressed in COS-7 cells. We report here that pro-IL-16 is most likely synthesized as a 67-kDa protein and is encoded from a major 2.6-kb tra nscript, Recombinant pro-IL-16 polypeptides are specifically cleaved i n lysates of CD8(+) cells, suggesting that the naturally secreted bioa ctive form of IL-16 is smaller than the originally published 130 amino acids fragment, Moreover, in contrast to other interleukins such as I L-15, IL-16 mRNA expression is almost exclusively limited to lymphatic tissues underlining the potential of IL-16 as an immune regulatory mo lecule.