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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Antigen Presenting Cell Biology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1525136

A Soluble Tapasin Isoform Disrupts Exogenous MHC I Antigen Presentation

Provisionally accepted
Wilfred Jefferies Wilfred Jefferies 1*Guillaume Hoeffel Guillaume Hoeffel 2Robyn Seipp Robyn Seipp 1Alex Moise Alex Moise 1Concepción Marañón Concepción Marañón 3Anne Hosmalin Anne Hosmalin 3Siri Lok Siri Lok 1Anne-Claire Ripoche Anne-Claire Ripoche 3
  • 1 University of British Columbia, Vancouver, Canada
  • 2 INSERM U1104 Centre d'immunologie de Marseille-Luminy (CIML), Marseille, Provence-Alpes-Côte d'Azur, France
  • 3 INSERM U1016 Institut Cochin, Paris, Île-de-France, France

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

    Antigen processing and presentation via the MHC Class I peptide loading complex (PLC) are crucial for initiating adaptive immune responses against pathogens and tumours. Tapasin, a key component of the PLC, is produced in multiple isoforms through alternative splicing, each isoform influencing the assembly and stability of MHC Class I molecules differently. While the canonical Tapasin isoform plays a critical role in stabilizing MHC Class I by facilitating optimal peptide loading in the endoplasmic reticulum (ER), the other isoforms function in distinct ways that impact immune regulation.Aims: This study aimed to investigate the role of Tapasin isoforms, particularly isoform 3, in modulating antigen presentation and immune responses, focusing on their effects on MHC Class I peptide loading and surface expression.Results: Our findings show that isoforms 1 and 2 stabilize TAP and facilitate efficient peptide loading onto MHC Class I in the ER, promoting optimal antigen presentation. In contrast, isoform 3, which lacks both the ER retention signal and the transmembrane domain, is secreted and acts as a negative regulator. Isoform 3 inhibits the loading of exogenous peptides onto MHC Class I molecules at the cell surface, possibly by interfering with peptide loading in the ER or through other intracellular mechanisms.

    Keywords: Antigen Presentation/Processing, MHC class I, Dendritic Cells, Cytotoxic T Cells, Tapasin

    Received: 08 Nov 2024; Accepted: 23 Dec 2024.

    Copyright: © 2024 Jefferies, Hoeffel, Seipp, Moise, Marañón, Hosmalin, Lok and Ripoche. 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: Wilfred Jefferies, University of British Columbia, Vancouver, Canada

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