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Passage of transmissible cancers in the Tasmanian devil is due to a dominant, shared peptide motif and a limited repertoire of MHC-I allotypes

A Gastaldello, SH Ramarathinam, A Bailey, R Owen, S Turner, A Kontouli, T Elliott, P Skipp, AW Purcell, HV Siddle
doi: https://doi.org/10.1101/2020.07.03.184416
A Gastaldello
1School of Biological Sciences, University of Southampton, Southampton, UK
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SH Ramarathinam
4Department of Biochemistry and Molecular Biology and the Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
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A Bailey
2Centre for Cancer Immunology, University of Southampton, Southampton, UK
3Institute for Life Sciences, University of Southampton, Southampton, UK
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R Owen
1School of Biological Sciences, University of Southampton, Southampton, UK
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S Turner
1School of Biological Sciences, University of Southampton, Southampton, UK
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A Kontouli
2Centre for Cancer Immunology, University of Southampton, Southampton, UK
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T Elliott
2Centre for Cancer Immunology, University of Southampton, Southampton, UK
3Institute for Life Sciences, University of Southampton, Southampton, UK
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P Skipp
1School of Biological Sciences, University of Southampton, Southampton, UK
3Institute for Life Sciences, University of Southampton, Southampton, UK
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AW Purcell
4Department of Biochemistry and Molecular Biology and the Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
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HV Siddle
1School of Biological Sciences, University of Southampton, Southampton, UK
3Institute for Life Sciences, University of Southampton, Southampton, UK
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  • For correspondence: h.v.siddle@soton.ac.uk
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Abstract

Transmissible cancers are spread via the passage of malignant cells. The survival of the Tasmanian devil, the largest marsupial carnivore, is threatened by two independent transmissible cancers, devil facial tumour (DFT) 1 and devil facial tumour 2 (DFT2). To aid the development of a peptide vaccine and to interrogate how histocompatibility barriers can be overcome, we analysed the peptides bound to Major Histocompatibility Complex class I molecules from the Tasmanian devil and its transmissible tumours. Comparison of the peptidomes from DFT1+IFNγ, DFT2 and host fibroblast cells demonstrates a shared motif, despite differences in MHC-I allotypes between the cell lines. Importantly, DFT1+IFNγ and DFT2 share the presentation of peptides derived from neural proteins, reflecting a common cellular origin that should be exploited for vaccine design. These results suggest that some polymorphisms between tumours and host are ‘hidden’ by a common peptide motif, providing the potential for permissive passage of infectious cells.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://www.ensembl.org/Sarcophilus_harrisii/Info/Index

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 04, 2020.
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Passage of transmissible cancers in the Tasmanian devil is due to a dominant, shared peptide motif and a limited repertoire of MHC-I allotypes
A Gastaldello, SH Ramarathinam, A Bailey, R Owen, S Turner, A Kontouli, T Elliott, P Skipp, AW Purcell, HV Siddle
bioRxiv 2020.07.03.184416; doi: https://doi.org/10.1101/2020.07.03.184416
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Passage of transmissible cancers in the Tasmanian devil is due to a dominant, shared peptide motif and a limited repertoire of MHC-I allotypes
A Gastaldello, SH Ramarathinam, A Bailey, R Owen, S Turner, A Kontouli, T Elliott, P Skipp, AW Purcell, HV Siddle
bioRxiv 2020.07.03.184416; doi: https://doi.org/10.1101/2020.07.03.184416

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