Identification of the first antagonist peptide that inhibits biological effects of interleukin-15
Abstract
Interleukin-15 (IL-15) is a pro-inflammatory cytokine that is expressed in several autoimmune and inflammatory diseases. We have identified the 36-45 sequence KVTAMKCFLL on human IL-15 that is recognized by a soluble form of recombinant hIL-15Ra-Fc fusion protein. This sequence synthesized as a 10 aa. peptide binds to the IL-15Raand was able to block the biological activity of IL-15 in two IL-15 dependent cells lines. Using alanine scan strategy we identified a more active peptide by replacing the second Lys in the sequence for the polar non-charged amino acid threonine. Moreover, soluble IL-15Rawas quantitated by a newly developed enzyme-linked immunosorbent assay (ELISA) using the P8 peptide as capture in samples of synovial fluid from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). This research won the 2012 Award of the Cuban National Academy of Sciences.