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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Antigen Presenting Cell Biology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1554561
Translation of bi-directional transcripts enhances MHC-I peptide diversity
Provisionally accepted
Filip Zavadil Kokas 1
Tomáš Henek 1
Justine Habault 2
René Chemali 3
Maria Camila Tovar-Fernadez 2 Chrysoula Daskalogianni 2 Laurence Malbert-Colas 2
Lixiao Wang 4 Sivakumar Vadivel Gnanasundram 4 Borek Vojtesek 1*
Lenka Hernychova 1*
Sebastien Apcher 3*
Robin Fahraeus 2*- 1 Masaryk Memorial Cancer Institute (MMCI), Brno, South Moravia, Czechia
- 2 Inserm UMRS1131, Institut de Génétique Moléculaire, Université Paris Cité, Hôpital St. Louis, paris, France
- 3 Institut Gustave Roussy, Villejuif, France
- 4 Department of Medical Biosciences, Faculty of Medicine, Umeå University, Umeå, Västerbotten, Sweden
Antisense transcripts play an important role in generating regulatory non-coding RNAs but whether these transcripts are also translated to generate functional peptides remains poorly understood. In this study, RNA sequencing and six-frame database generation were combined with mass spectrometry analysis of peptides isolated from polysomes to identify Nascent Pioneer Translation Products (Na-PTPs) originating from alternative reading frames of bi-directional transcripts. Two Na-PTP originating peptides derived from antisense strands stimulated CD8+ T cell proliferation when presented to peripheral blood mononuclear cells (PBMCs) from nine healthy donors. Importantly, an antigenic peptide derived from the reverse strand of two cDNA constructs was presented on MHC-I molecules and induced CD8+ T cell activation. The results demonstrate that three-frame translation of bi-directional transcripts generates antigenic peptide substrates for the immune system. This discovery holds significance for understanding the origin of self-discriminating peptide substrates for the major histocompatibility class I (MHC-I) pathway and for enhancing immune-based therapies against infected or transformed cells.
Keywords: MHC-I epitope, Pionner translational products, bi-directional transcripts, Bi-directinal translation, reverse strand antigenic peptides
Received: 02 Jan 2025; Accepted: 25 Feb 2025.
Copyright: © 2025 Zavadil Kokas, Henek, Habault, Chemali, Tovar-Fernadez, Daskalogianni, Malbert-Colas, Wang, Gnanasundram, Vojtesek, Hernychova, Apcher and Fahraeus. 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:
Borek Vojtesek, Masaryk Memorial Cancer Institute (MMCI), Brno, 656 53, South Moravia, Czechia
Lenka Hernychova, Masaryk Memorial Cancer Institute (MMCI), Brno, 656 53, South Moravia, Czechia
Sebastien Apcher, Institut Gustave Roussy, Villejuif, France
Robin Fahraeus, Inserm UMRS1131, Institut de Génétique Moléculaire, Université Paris Cité, Hôpital St. Louis, paris, France
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