High- throughput screening for class I peptide MHC binding via yeast surface display

• 成果类型: Article
• 署名作者: Holec, Patrick, V; Breuckman, Kathryn C.; Leddy, Owen; White, Forest M.; Bryson, Bryan D.; Birnbaum, Michael E.
• 署名单位: Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Ragon Institute; Harvard University Medical Affiliates; Massachusetts General Hospital
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2514741122
• 发表日期: 2025-11-25
• 页码: e2514741122
• 关键词: yeast display; peptide-MHC; antigen presentation; antigen; specificity; predictions; STABILITY; molecules

摘要

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 systematically evaluate stable peptide presentation across diverse MHC alleles. Here, we describe a yeast display pipeline that can be deployed to rapidly screen peptides to identify class I pMHC binders across many alleles. Through this, we isolate unique biological phenomena such as alteration of the peptide presentation of HLA-B57 via interaction with the antiviral small molecule abacavir. We apply this approach to multiple pathogen proteomes (Mycobacterium tuberculosis Type VII secretion substrates, SARS-CoV-2, Dengue, and Zika) to create a comprehensive list of potential T cell antigens. Altogether, this platform acts as a flexible tool to generate large unbiased datasets for class I peptide binding at a speed and scale competitive with the biological systems they represent.