The Production of Recombinant Immunoglobulin Superfamily Proteins in the Yeast Saccharomyces Cerevisiae

Abstract

135 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1999.Although scFvs and scTCRs are structurally homologous, they have very distinct expression and stability behaviors. In fact, in order to develop an efficient scTCR production strategy like that developed for scFvs, it was necessary to alter the characteristics of the protein itself to improve its processing and stability characteristics. These properties were improved using a directed evolution approach and yeast surface display. Evolution resulted in a super-scTCR scaffold with optimized secretion, solubility, and stability properties. This scaffold will, for the first time, enable directed evolution of the binding properties of the scTCR for its peptide/MHC ligand. The results described in this thesis illustrate the power of combining genetic, cellular, and protein engineering tools for improving the secretion and stability characteristics of a target protein.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD