The Journal of Immunology, Vol 146, Issue 3 915-919, Copyright © 1991 by American Association of Immunologists

ARTICLES

A chimeric IL-2/Ig molecule possesses the functional activity of both proteins

NF Landolfi
Protein Design Labs, Inc., Mountain View, CA 94043.

An expression vector (pIL-2/IgG1) was constructed with the coding sequence of human IL-2 inserted upstream of the four exons (CH1, hinge, CH2, and CH3) that encode the human IgG1 H chain constant region. Introduction of this vector into a nonsecreting murine myeloma cell line resulted in the production of a chimeric molecule (IL-2/IgG1) consisting of IL-2 attached to the three Ig constant region domains. This molecule was secreted by the transfectant as a homodimer. Functional characterization revealed that the IL-2/IgG1 chimeric molecule exhibited the binding and proliferation-mediating activities of IL-2. On a per molecule basis, IL-2/IgG1 was indistinguishable from human rIL-2 in the ability to induce the proliferation of an IL-2- dependent T cell line. This chimeric molecule also possesses Ig effector function, in that it can mediate the specific lysis of IL-2R- positive cells in the presence of complement. These results demonstrate that it is possible to maintain Ig effector function in molecules ("immunoligands") in which the binding specificity is conferred not by Ig variable regions, but rather, by a ligand of choice.

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