ArticlebioRxiv : the preprint server for biology2025
High-throughput screening for class I peptide MHC binding via yeast surface display.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
T cells rely on short peptides presented by highly polymorphic major histocompatibility complexes (MHCs) to selectively initiate adaptive immune responses. Despite its importance, few techniques can systemically evaluate stable peptide presentation across diverse MHC alleles. Here, we describe a yeast display pipeline that can be deployed to rapidly screen proteomic space to identify class I pMHC binders across many alleles. Through this, we capture unique biological phenomena such as interference with peptide presentation via type IV drug-induced hypersensitivity. We apply this approach to multiple pathogen proteomes (Mtb Type 7S substrates, SARS-CoV-2, Dengue, and Zika) to create a high-resolution catalog of potential T cell antigens. Altogether, this platform acts as a flexible tool to generate large unbiased datasets for class I peptide presentation at a speed and scale competitive with the biological systems they represent.
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