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Class II transactivator induces expression of MHC-I and MHC-II in transmissible Tasmanian devil facial tumours

Citation

Ong, CEB and Cheng, V and Siddle, HV and Lyons, AB and Woods, GM and Flies, AS, Class II transactivator induces expression of MHC-I and MHC-II in transmissible Tasmanian devil facial tumours, Open biology, 12, (10) Article 220208. ISSN 2046-2441 (2022) [Refereed Article]


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Copyright Statement

2022. The Authors. This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License (https://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

DOI: doi:10.1098/rsob.220208

Abstract

MHC-I and MHC-II molecules are critical components of antigen presentation and T cell immunity to pathogens and cancer. The two monoclonal transmissible devil facial tumours (DFT1, DFT2) exploit MHC-I pathways to overcome immunological anti-tumour and allogeneic barriers. This exploitation underpins the ongoing transmission of DFT cells across the wild Tasmanian devil population. We have previously shown that the overexpression of NLRC5 in DFT1 and DFT2 cells can regulate components of the MHC-I pathway but not MHC-II, establishing the stable upregulation of MHC-I on the cell surface. As MHC-II molecules are crucial for CD4+ T cell activation, MHC-II expression in tumour cells is beginning to gain traction in the field of immunotherapy and cancer vaccines. The overexpression of Class II transactivator in transfected DFT1 and DFT2 cells induced the transcription of several genes of the MHC-I and MHC-II pathways. This was further supported by the upregulation of MHC-I protein on DFT1 and DFT2 cells, but interestingly MHC-II protein was upregulated only in DFT1 cells. This new insight into the regulation of MHC-I and MHC-II pathways in cells that naturally overcome allogeneic barriers can inform vaccine, immunotherapy and tissue transplant strategies for human and veterinary medicine.

Item Details

Item Type:Refereed Article
Keywords:CIITA, MHC-I, major histocompatibility, Tasmanian devil, immunology
Research Division:Agricultural, Veterinary and Food Sciences
Research Group:Veterinary sciences
Research Field:Veterinary immunology
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the agricultural, food and veterinary sciences
UTAS Author:Ong, CEB (Dr Chrissie Ong)
UTAS Author:Lyons, AB (Associate Professor Bruce Lyons)
UTAS Author:Woods, GM (Professor Gregory Woods)
UTAS Author:Flies, AS (Dr Andy Flies)
ID Code:154358
Year Published:2022
Funding Support:Australian Research Council (DE180100484)
Deposited By:Menzies Institute for Medical Research
Deposited On:2022-11-25
Last Modified:2022-12-16
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