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REVIEW article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1540431

Unlocking the Secrets of the Immunopeptidome: MHC Molecules, ncRNA Peptides, and Vesicles in Immune Response

Provisionally accepted
Arpita Balakrishnan Arpita Balakrishnan 1,2Gabriela Winiarek Gabriela Winiarek 1Olga Hołówka Olga Hołówka 1Jakub Godlewski Jakub Godlewski 3Agnieszka Bronisz Agnieszka Bronisz 1*
  • 1 Tumor Microenvironment Laboratory, Mossakowski Medical Research institute, Warsaw, Poland
  • 2 Translational Medicine Doctoral School, Centre of Postgraduate Medical Education, Warsaw, Poland
  • 3 Department of Neurooncology, Mossakowski Medical Research Institute, Warsaw, Poland

The final, formatted version of the article will be published soon.

    The immunopeptidome, a diverse set of peptides presented by Major Histocompatibility Complex (MHC) molecules, is a critical component of immune recognition and response. This review article delves into the mechanisms of peptide presentation by MHC molecules, particularly emphasizing the roles of ncRNA-derived peptides and extracellular vesicles (EVs) in shaping the immunopeptidome landscape. We explore established and emerging insights into MHC molecule interactions with peptides, including the dynamics of peptide loading, transport, and the influence of cellular and genetic variations. The article highlights novel research on non-coding RNA (ncRNA)-derived peptides, which challenge conventional views of antigen processing and presentation and the role of EVs in transporting these peptides, thereby modulating immune responses at remote body sites. This novel research not only challenges conventional views but also opens up new avenues for understanding immune responses. Furthermore, we discuss the implications of these mechanisms in developing therapeutic strategies, particularly for cancer immunotherapy. By conducting a comprehensive analysis of current literature and advanced methodologies in immunopeptidomics, this review aims to deepen the understanding of the complex interplay between MHC peptide presentation and the immune system, offering new perspectives on potential diagnostic and therapeutic applications. Additionally, the interactions between ncRNA-derived peptides and EVs provide a mechanism for the enhanced surface presentation of these peptides and highlight a novel pathway for their systemic distribution, potentially altering immune surveillance and therapeutic landscapes.

    Keywords: Immunopeptidome, MHC molecules, ncRNA-Derived Peptides, Extracellular vesicles (EVs), cancer immunotherapy

    Received: 05 Dec 2024; Accepted: 13 Jan 2025.

    Copyright: © 2025 Balakrishnan, Winiarek, Hołówka, Godlewski and Bronisz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Agnieszka Bronisz, Tumor Microenvironment Laboratory, Mossakowski Medical Research institute, Warsaw, Poland

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.