Multi-chain eukaryotic display vectors and uses thereof

摘要

A eukaryotic expression vector capable of displaying a multi-chain polypeptide on the surface of a host cell is provided, such that the biological activity of the multi-chain polypeptide is exhibited at the surface of the host cell. Such a vector allows for the display of complex biologically active polypeptides, e.g., biologically active multi-chain polypeptides such as immunoglobulin Fab fragments. The present invention describes and enables the successful display of a multi-chain polypeptide on the surface of a eukaryotic host cell. Preferred vectors are described for expressing the chains of a multi-chain polypeptide in a host cell separately and independently (e.g., under separate vector control elements, and/or on separate expression vectors, thus forming a matched vector set). The use of such matched vector sets provides flexibility and versatility in the generation of eukaryotic display libraries, for example the ability to generate and to display multi-chain polypeptides by combining and recombining vectors that express variegations of the individual chains of a multi-chain polypeptide. Entire repertoires of novel chain combinations can be devised using such vector sets.

主权项

1. A multi-chain protein display library, comprising a plurality of multi-chain proteins each comprising at least two polypeptide chains, wherein the multi-chain proteins are displayed on a surface of yeast host cells, and wherein the multi-chain proteins are multi-chain T cell receptors, multi-chain MHC class I molecules, multi-chain MHC class II molecules, multi-chain immunoglobulin molecules, or multi-chain biologically active fragments thereof, wherein the multi-chain immunoglobulin molecules each comprise a heavy chain variable region (VH) and a light chain variable region (VL), which are on separate chains.