INTERACTION OF THE PRE-DOMAIN OF INTERLEUKIN-1 WITH THE MATURE DOMAIN

The two interleukin 1 precursors (preIL-1 alpha and beta) with a molec ular mass of 33 kDa are proteolytically processed to the mature carbox yl-terminal 17-kDa proteins, In this study we newly developed a monocl onal antibody against the precursor domain of IL-1 beta (ED7), of whic h the binding to preIL-1 beta was hindered by a polyclonal antibody ag ainst the mature domain of IL-1 beta, Immunoprecipitation of limited p roteolysed preIL-1 beta by ED7 suggested that the epitope for ED7 may not be localized at the junction between preIL-1 beta and mature IL-1 beta. We therefore examined the possibility that the pre-domain of IL- 1 beta might interact with the mature domain by using chemical cross-l inking. V8 protease yielded a mature 17.5-kDa protein from untreated p reIL-1 beta, but not chemically cross-linked preIL-1 beta. However, cl eavage of the cross-link with a-mercaptoethanol liberated a mature 17. 5-kDa protein from preIL-1 beta, suggesting that the pre-domains of IL -1 beta might interact with the mature domain, Similar phenomena were observed with preIL-1 alpha. Such an intermolecular interaction may in hibit or modulate the biological activity of mature IL-1s.