Solution mapping of MHC- I:TCR interactions using a minimalistic protein system

• 成果类型: Article
• 署名作者: Woodward, Claire H.; Chaudhuri, Apala; Chen, Xiaojing Tina; White, William L.; Garcia, K. Christopher; Baker, David; Sgourakis, Nikolaos G.
• 署名单位: University of Pennsylvania; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; Stanford University; Stanford University; Stanford University; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9882
• DOI: 10.1073/pnas.2506016122
• 发表日期: 2025-06-09
• 关键词: cell-receptor docking; chemical-shift; antigen; RECOGNITION; complexes; peptides; DESIGN

摘要

Recognition of epitopic peptide antigens presented on class I major histocompatibility complex (MHC- I) proteins by T cell receptors (TCRs) forms the cornerstone of immune surveillance, leading to a plethora of adaptive immune responses. Characterization of TCR:peptide/MHC- I interactions is critical for understanding immune recognition, and developing immunotherapies, but the large variation in docking orientations of TCRs on their peptide/MHC- I targets challenges structural modeling. NMR spectroscopy could potentially resolve this ambiguity, but the large size of the TCR:peptide/MHC- I complex limits data quality. Here, we demonstrate that a designed MHC- I protein, SMART A*02:01, enables facile solution mapping of MHC- I:TCR interactions at scale. Our approach can be combined with computational modeling and structure- guided engineering to aid the development of TCR- based therapeutics.