Rhesus macaque Interleukin-16 (rMamu IL-6)

IL-16 is essentially a chemokine that binds to CD4 and induces chemotaxis of all cells bearing the CD4 receptor. IL-16 is constitutively synthesized by CD8+ T cells as a bioactive molecule. Although, CD4+ T cells constitutively express IL-16 mRNA and the putative peptide precursor (proIL-16), they do not express detectable intracellular levels of the preformed bioactive protein. CD8+ T cells release functional IL-16 peptides upon exposure to histamine, serotonin, antigens, mitogens or anti-CD3. This release is preceded by cleavage of the C-terminal region by caspase-3. Mechanisms for CD4-specific processing and release of mature IL-16 are largely unknown. However, antigenic co-stimulation of CD4+ T cells with CD3/CD28 mAbs can result in the release of bioactive IL-16. IL-16's characteristic CD4-dependent chemotaxis is accompanied by signal transduction pathways that involve activation of p56lck, increases in intracellular calcium, inositol triphosphate generation, activation of phosphoinositide 3-kinase, and translocation of protein kinase C. These signaling events culminate in increased expression of MHC II molecules and CD25 on resting T lymphocytes. Conversely, IL-16 also inhibits mixed lymphocyte reactions and has also been reported to inhibit the transcription of HIV/SIV in vitro.

r Mamu IL-16 cDNA code for a 130 aa polypeptide representing most of the processed form of secreted IL-16 that is 97.7% homologous to human IL-16 (Lee et al, AIDS Res & Hum Retrov 1998 14:1323-1328). This results in monomers of approximately 20 kDa, although the active form of the molecule depends on its tetrameric organization.

rMamu IL-16 is produced as a mature polypeptide in E coli using the pET14B expression vector with a thrombin digestion site leaving an additional Gly-Ser-His residues at the aminoterminus.

Purity is verified by PAGE electrophoresis and absence of endotoxin by LAL test.

Bioactivity of each lot is tested based on induction of chemotaxis of CD4+ cells.

Half-life of rMamu IL-16 in vivo following subcutaneous administration was found to be approximately 24 hours.