THE FUNCTIONAL DISPLAY OF INTERLEUKIN-2 ON FILAMENTOUS PHAGE

We report the novel display of interleukin-a (IL-2) and an IL-2 analog , D126, on the surface of filamentous bacteriophage using a phagemid v ector system, A synthetic human IL-2 gene and its D126 analog were fus ed to the carboxyl-terminal domain of the gene III minor phage coat pr otein. Expression of IL-2 and D126 was verified by their reactivity wi th an IL-a-specific antibody, Biological response of IL-2 phage on mur ine CTLL-2 cells was comparable to that of recombinant soluble IL-2, w hile the D126 phage displayed a reduced biological response similar to that previously measured by soluble D126 protein. Biosensor surface p lasmon resonance was employed to verify binding of the IL-2 and D126 p hage to the IL-2 alpha beta cc receptor complex, A 41-fold enrichment of IL-2 phage over R408 helper phage was demonstrated in biopanning af finity selection studies employing biotinylated alpha beta cc receptor complex, These biopanning studies are the first reports of affinity s election of IL-2 phage and demonstrate a novel use for the alpha beta cc receptor complex, Together, these studies confirm that the structur al integrity of IL-2 and D126 is maintained when they are displayed as a gIIIp fusion protein on phage particles and provide the foundation for further selection studies employing IL-2 analog phage libraries. ( C) 1997 Academic Press.