Introduction to Antibody Affinity Maturation by Yeast Display

At present, many companies are utilizing yeast display technology for antibody drug development research, and many drugs developed based on yeast demonstration technology have been marketed. These antibody drugs have good therapeutic effects and safety in the clinic. Yeast display technology has a wide range of roles in the process of antibody development. Based on our rich field experience and yeast display platform, Creative Biolabs provides comprehensive services to support antibody discovery by yeast display.

Antibody Affinity Maturation by Yeast Display

Yeast display system technology was pioneered by Boder and Wittrup in 1997. In yeast display systems, foreign proteins are displayed on the yeast surface by fusion with yeast cell wall proteins. Yeast contains a 200 nm-thick cell wall consisting of β-polysaccharides, mannoproteins, and chitin. The inner surface of the yeast cell wall prevents the penetration of macromolecules by forming a skeleton layer of tightly chitosan-linked β-1, 3-glucan microfibers. For yeast display technology, yeast display library construction and yeast display library screening are of paramount importance and determine the results of subsequent studies.

Different yeast strains are widely used to display various proteins, peptides, and antibodies, but the Saccharomyces cerevisiae Aga1-Aga2 based yeast display system is the most popular one. It has a 10⁹ storage capacity. The principle of this approach is based on the expression of a foreign protein fused to the Aga2 protein. The Aga2 protein itself is anchored to the cell membrane with the Aga1 protein via two disulfide bonds, thereby forming a covalent complex on the yeast surface.

Due to its unique advantages, yeast display systems are commonly used in human monoclonal antibody identification, antibody affinity maturation, and yeast display-based T cell receptor engineering. The most immediate advantage of yeast display is the precise control of selection parameters during screening by flow cytometric fluorescent sorting techniques. The percentage of the population collected, signal normalization, and the required binding affinity can be demarcated by flow cytometry. This ability to define binding criteria during selection has advantages over phage display platforms, where variant identification relies on washing steps rather than real-time kinetic observations. The yeast surface display screening method is compatible with the quantitative and multiparameter analysis provided by flow cytometry. It provides precise control over conditions such as buffer composition, pH, temperature, and antigen concentration to sort clones that bind to target proteins under specific incubation conditions. For example, it can sort clones with increased stability under specific conditions. It can analyze each cell in the library one by one to get a real-time view of the display level and its antigen binding and to sort out specific cell populations. Specifically, phage screening for high affinity clones is done by increasing the selection pressure such as the concentration of encapsulated antigen, washing intensity, etc., but it does not allow effective monitoring, while the screened clones can only be distinguished from the positives, not the affinity level, and the affinity comparison can only be done after the protein is expressed, which results in a large amount of workload and high cost. Yeast display is to incubate the libraries to be sorted by different concentrations of target proteins, and then differentiate the antibody display clones with different affinities at a certain incubation concentration of target proteins and sort them on demand.

Creative Biolabs has a wealth of knowledge and experience in yeast display. We would be happy to share with you our knowledge and experience on antibody affinity maturation by yeast display.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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