Recombinant hydrophilic region of murine retroviral protein p15E inhibits stimulated T-lymphocyte proliferation.

Abstract

Retroviral envelope protein p15E and antigenically related proteins have been implicated as potential mediators of immune dysfunction associated with retroviral infections and with neoplasia. Due to its extreme hydrophobicity, purified p15E has not been available in a nondenatured form or in sufficient quantities for detailed studies on the mechanisms of its immunosuppressive effects. Therefore, a plasmid was constructed to direct the synthesis in Escherichia coli of the major hydrophilic region of murine p15E. The purified recombinant p15E derivative, soluble under physiological conditions, inhibited by up to 60% (EC50 = 7.5 nM) the anti-CD3-driven proliferation of human T lymphocytes but had no effect on the proliferation of the transformed T-cell line Jurkat. The recombinant protein also inhibited, by up to an average of 92% (EC50 = 2.1 microM), the proliferation of the murine T-cell line CTLL-2. These data (i) provide direct evidence that a retroviral envelope protein can itself inhibit lymphoproliferative function and (ii) map the inhibitory activity to a specific region of p15E. The availability of soluble, recombinant p15E should facilitate studies of the pathogenesis of the immunosuppression accompanying retroviral infections and neoplastic diseases.