Ubiquitin-like moiety of the monoclonal nonspecific suppressor factor beta is responsible for its activity.

Abstract

Monoclonal nonspecific suppressor factor (MNSF), a lymphokine produced by murine T cell hybridoma, possesses pleiotrophic Ag-nonspecific suppressive functions. Most recently, a cDNA clone encoding MNSF beta (a subunit of MNSF) was isolated and characterized. The MNSF beta cDNA encodes a 14.5-kDa fusion protein with MNSF-like activity consisting of an 8-kDa ubiquitin-like segment (ubi-L) and the ribosomal protein S30 (6.5 kDa). To determine whether ubi-L itself has biologic activity, cDNA encoding the ubi-L region was expressed in bacteria and the recombinant product was tested for the activity. Ubi-L showed MNSF-like biologic activity without any cytotoxic action. Interestingly, the addition of ubiquitin to the assay inhibited ubi-L-induced suppression. IFN-gamma, which is known to enhance the expression of MNSF receptor, induced splenocytes to secrete ubi-L by increasing mRNA. Ubi-L has species-specific action and the ability to selectively inhibit the B cell proliferative response stimulated by soluble but not by Sepharose-bound anti-Ig Ab. In addition, okadaic acid, a serine/threonine phosphatase 1 and 2A inhibitor, showed a synergistic inhibitory action with ubi-L, indicative of the possible involvement of phosphatase(s) in the regulation of ubi-L action.