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Updated: Apr 11, 2026

Protein Engineering by Yeast Surface Display

Protein Engineering by Yeast Surface Display

Published on: November 29, 2024

T Cell Receptor Engineering and Analysis Using the Yeast Display Platform.

Sheena N Smith¹, Daniel T Harris, David M Kranz

¹Department of Biochemistry, University of Illinois, 600 S. Matthews Ave., Urbana, IL, 61801, USA.

Methods in Molecular Biology (Clifton, N.J.)

|June 11, 2015

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Researchers engineered single-chain T cell receptors (TCRs) using yeast display to enhance their affinity for therapeutic applications. This method allows rapid analysis of TCR binding features for targeting intracellular antigens.

Area of Science:

Immunology
Molecular Biology
Biotechnology

Background:

The T cell receptor (TCR) recognizes peptide-MHC complexes, crucial for sensing intracellular antigens and orchestrating immune responses.
Despite high sensitivity, TCRs exhibit low affinity for peptide-MHC ligands, limiting their therapeutic potential.
Engineering TCR affinity could broaden their application for targeting intracellular antigens, similar to antibody-based therapies.

Purpose of the Study:

To describe methods for engineering and analyzing single-chain TCRs (scTCRs) using a yeast display platform.
To enable rapid affinity maturation and characterization of scTCRs for potential therapeutic use.
To overcome the limitations of low natural TCR affinity for therapeutic targeting.

Main Methods:

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Last Updated: Apr 11, 2026

Protein Engineering by Yeast Surface Display

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Utilized a yeast display system for expressing and engineering single-chain T cell receptors (scTCRs).

Developed scTCRs analogous to antibody scFv fragments for affinity maturation against various peptide-MHC ligands.

Employed yeast display for rapid generation and analysis of scTCR variants, assessing specificity and affinity without protein purification.

Main Results:

Demonstrated the feasibility of engineering scTCRs with improved binding characteristics.
Showcased the yeast display system's efficiency in rapidly generating and analyzing diverse scTCR variants.
Established a platform for affinity maturation of TCRs against a wide range of peptide-MHC targets.

Conclusions:

Yeast display is an effective platform for engineering and analyzing single-chain TCRs.
scTCRs engineered via yeast display hold promise for therapeutic applications targeting intracellular antigens.
This approach facilitates the development of novel immunotherapies by overcoming natural TCR affinity limitations.