Recruiting ESCRT to single-chain heterotrimer peptide MHCI releases antigen-presenting vesicles that stimulate T cells selectively

• 成果类型: Article
• 署名作者: Olson, Blade A.; Huey-Tubman, Kathryn E.; Mao, Zhiyuan; Hoffmann, Magnus A. G.; Bjorkman, Pamela J.; Murray, Richard M.; Mayo, Stephen L.
• 署名单位: California Institute of Technology; University of California System; University of California Los Angeles; David Geffen School of Medicine at UCLA; California Institute of Technology; University of California System; University of California San Francisco; The J David Gladstone Institutes; University of California System; University of California San Francisco
• 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.2501046122
• 发表日期: 2025-12-23
• 页码: 2501046122
• 关键词: antigen-presenting vesicles; peptide major histocompatibility complexes; autoimmune disease; cell-free immunoregulation; membrane-vesicles; lymphocytes; molecules; activation; STABILITY; naive

摘要

Immune cells naturally secrete extracellular antigen-presenting vesicles (APVs) displaying peptide:MHC complexes to facilitate the initiation, expansion, maintenance, or silencing of immune responses. Previous work has sought to manufacture and purify these vesicles for cell-free immunotherapies. In this study, APV assembly and release is achieved in nonimmune cells by transfecting a single-chain heterotrimer (SCT) peptide major histocompatibility complex I (pMHCI) construct containing an ESCRT-and ALIX-binding region (EABR) sequence appended to the cytoplasmic tail; this EABR sequence recruits ESCRT proteins to induce the budding of APVs displaying SCT pMHCI. A comparison of multiple pMHCI constructs shows that inducing the release of APVs by the addition of an EABR sequence generalizes across SCT pMHCI constructs. Purified pMHCI/EABR APVs selectively stimulate IFN-gamma release from T cells presenting their cognate T cell receptor, demonstrating the potential use of these vesicles as a form of cell-free immunotherapy.