PT  - JOURNAL ARTICLE
AU  - Brooke D. Huisman
AU  - Zheng Dai
AU  - David K. Gifford
AU  - Michael E. Birnbaum
TI  - A high-throughput yeast display approach to profile pathogen proteomes for MHC-II binding
AID  - 10.1101/2022.02.22.480950
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.02.22.480950
4099  - http://biorxiv.org/content/early/2022/02/24/2022.02.22.480950.short
4100  - http://biorxiv.org/content/early/2022/02/24/2022.02.22.480950.full
AB  - T cells play a critical role in the adaptive immune response, recognizing peptide antigens presented on the cell surface by Major Histocompatibility Complex (MHC) proteins. While assessing peptides for MHC binding is an important component of probing these interactions, traditional assays for testing peptides of interest for MHC binding are limited in throughput. Here we present a yeast display-based platform for assessing the binding of tens of thousands of user-defined peptides in a high throughput manner. We apply this approach to assess a tiled library covering the SARS-CoV-2 proteome and four dengue virus serotypes for binding to human class II MHCs, including HLA-DR401, -DR402, and -DR404. This approach identifies binders missed by computational prediction and serves as a framework for diverse objectives, including examining relationships between viral conservation and MHC binding.Competing Interest StatementD.K.G. is a founder of ThinkTx. M.E.B. is an equity holder in 3T Biosciences, and is a co-founder of Viralogic Therapeutics and Abata Therapeutics. The other authors declare no competing interests.