Ae. Morris et al., Incorporation of an isoleucine zipper motif enhances the biological activity of soluble CD40L (CD154), J BIOL CHEM, 274(1), 1999, pp. 418-423
Recent progress in the understanding of immune function indicates that the
interaction of CD40L with its receptor, CD40, plays a pivotal role in both
humoral immunity and cell-mediated defense against pathogens. Functional st
udies of this interaction on both dendritic cells and malignant cells have
demonstrated that CD40L also plays an important role in immune surveillance
and anti-tumor immunity. CD40L exists in nature predominantly as a membran
e-anchored molecule. To develop CD40L as a potential therapeutic, it is imp
ortant to optimize soluble forms of this molecule that could be used in a c
linical setting. Several reports have shown that soluble forms of CD40L, li
ke CD40 antibodies, are biologically active. In the present report we demon
strate that the incorporation of an isoleucine zipper trimerization motif s
ignificantly enhances the biological activity of soluble CD40L.