Design of high-specificity binders for peptide–MHC-I complexes

Liu, Bingxu; Greenwood, Nathan; Bonzanini, Julia E.; Motmaen, Amir; Meyerberg, Jeremy; Dao, Tao; Xiang, Xinyu; Ault, Russell; Sharp, Jazmin; Wang, Chunyu; Visani, Gian Marco; Vafeados, Dionne; Roullier, Nicole; Nourmohammad, Armita; Scheinberg, David A.; García, K. Christopher; Baker, David

doi:10.1126/science.adv0185

articleScienceJul 24, 2025HYBRID OA

Design of high-specificity binders for peptide–MHC-I complexes

BLBingxu Liu NGNathan Greenwood JEJulia E. Bonzanini AMAmir Motmaen JMJeremy Meyerberg

University of Washington · Memorial Sloan Kettering Cancer Center · +8 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

Class I major histocompatibility complex (MHC-I) molecules present peptides derived from intracellular antigens on the cell surface for immune surveillance. Proteins that recognize peptide-MHC-I (pMHCI) complexes with specificity for diseased cells could have considerable therapeutic utility. Specificity requires recognition of outward-facing amino acid residues within the disease-associated peptide as well as avoidance of extensive contacts with ubiquitously expressed MHC. We used RFdiffusion to design pMHCI-binding proteins that make extensive contacts with the peptide and identified specific binders for 11 target pMHCs starting from either experimental or predicted pMHCI structures. Upon incorporation into…

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43

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FWCI: 25.87
Percentile: 100%
References: 37

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Topics & keywords

Topics

Keywords

Major histocompatibility complex
Peptide
Antigen
MHC class I
Biology
MHC restriction
T-cell receptor
Cell biology

UN Sustainable Development Goals

Good health and well-being

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