The immunopeptidomes of two transmissible cancers and their host have a common, dominant peptide motif
The immunopeptidomes of two transmissible cancers and their host have a common, dominant peptide motif
Transmissible cancers are malignant cells that can spread between individuals of a population, akin to both a parasite and a mobile graft. The survival of the Tasmanian devil, the largest remaining marsupial carnivore, is threatened by the remarkable emergence of two independent lineages of transmissible cancer, devil facial tumour (DFT) 1 and devil facial tumour 2 (DFT2). To aid the development of a vaccine and to interrogate how histocompatibility barriers can be overcome, we analysed the peptides bound to major histocompatibility complex class I (MHC-I) molecules from Tasmanian devil cells and representative cell lines of each transmissible cancer. Here, we show that DFT1 + IFN-γ and DFT2 cell lines express a restricted repertoire of MHC-I allotypes compared with fibroblast cells, potentially reducing the breadth of peptide presentation. Comparison of the peptidomes from DFT1 + IFNγ, DFT2 and host fibroblast cells demonstrates a dominant motif, despite differences in MHC-I allotypes between the cell lines, with preference for a hydrophobic leucine residue at position 3 and position Ω of peptides. DFT1 and DFT2 both present peptides derived from neural proteins, which reflects a shared cellular origin that could be exploited for vaccine design. These results suggest that polymorphisms in MHC-I molecules between tumours and host can be ‘hidden’ by a common peptide motif, providing the potential for permissive passage of infectious cells and demonstrating complexity in mammalian histocompatibility barriers.
MHC, Tasmanian devil, Transmissible cancer, contagious cancer, immunopeptidome, marsupial
169-184
Gastaldello, A
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Ramarathinam, S H
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Bailey, A
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Owen, R
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Turner, S
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Kontouli, A
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Elliott, T
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Skipp, P
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Purcell, A W
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Siddle, H V
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June 2021
Gastaldello, A
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Ramarathinam, S H
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Bailey, A
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Owen, R
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Turner, S
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Kontouli, A
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Elliott, T
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Skipp, P
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Purcell, A W
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Siddle, H V
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Gastaldello, A, Ramarathinam, S H, Bailey, A, Owen, R, Turner, S, Kontouli, A, Elliott, T, Skipp, P, Purcell, A W and Siddle, H V
(2021)
The immunopeptidomes of two transmissible cancers and their host have a common, dominant peptide motif.
Immunology, 163 (2), .
(doi:10.1111/imm.13307).
Abstract
Transmissible cancers are malignant cells that can spread between individuals of a population, akin to both a parasite and a mobile graft. The survival of the Tasmanian devil, the largest remaining marsupial carnivore, is threatened by the remarkable emergence of two independent lineages of transmissible cancer, devil facial tumour (DFT) 1 and devil facial tumour 2 (DFT2). To aid the development of a vaccine and to interrogate how histocompatibility barriers can be overcome, we analysed the peptides bound to major histocompatibility complex class I (MHC-I) molecules from Tasmanian devil cells and representative cell lines of each transmissible cancer. Here, we show that DFT1 + IFN-γ and DFT2 cell lines express a restricted repertoire of MHC-I allotypes compared with fibroblast cells, potentially reducing the breadth of peptide presentation. Comparison of the peptidomes from DFT1 + IFNγ, DFT2 and host fibroblast cells demonstrates a dominant motif, despite differences in MHC-I allotypes between the cell lines, with preference for a hydrophobic leucine residue at position 3 and position Ω of peptides. DFT1 and DFT2 both present peptides derived from neural proteins, which reflects a shared cellular origin that could be exploited for vaccine design. These results suggest that polymorphisms in MHC-I molecules between tumours and host can be ‘hidden’ by a common peptide motif, providing the potential for permissive passage of infectious cells and demonstrating complexity in mammalian histocompatibility barriers.
Text
imm.13307 (1)
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Accepted/In Press date: 4 January 2021
e-pub ahead of print date: 18 January 2021
Published date: June 2021
Additional Information:
Funding Information:
This work was funded by the Research Project Grant, RPG-2015-103, from the Leverhulme Trust to HVS, AWP and TE. AB is funded by the CRUK Centres Network Accelerator Award A21998, TE is funded by CRUK Programme Grant A28279, and RO is funded by a Morris Animal Foundation Fellowship (D19ZO-413). Instrumentation in the Centre for Proteomic Research, University of Southampton, is supported by the BBSRC (BM/M012387/1) and the Wessex Medical Trust. The authors acknowledge the Monash Proteomics & Metabolomics Facility for the provision of mass spectrometry instrumentation and technical support. AWP is supported by the NHMRC Principal Research Fellowship 1137739. Computational resources were supported by the R@CMon/Monash Node of the NeCTAR Research Cloud, an initiative of the Australian Government?s Super Science Scheme and the Education Investment Fund.
Funding Information:
This work was funded by the Research Project Grant, RPG‐2015‐103, from the Leverhulme Trust to HVS, AWP and TE. AB is funded by the CRUK Centres Network Accelerator Award A21998, TE is funded by CRUK Programme Grant A28279, and RO is funded by a Morris Animal Foundation Fellowship (D19ZO‐413). Instrumentation in the Centre for Proteomic Research, University of Southampton, is supported by the BBSRC (BM/M012387/1) and the Wessex Medical Trust. The authors acknowledge the Monash Proteomics & Metabolomics Facility for the provision of mass spectrometry instrumentation and technical support. AWP is supported by the NHMRC Principal Research Fellowship 1137739. Computational resources were supported by the R@CMon/Monash Node of the NeCTAR Research Cloud, an initiative of the Australian Government’s Super Science Scheme and the Education Investment Fund.
Publisher Copyright:
© 2021 The Authors. Immunology published by John Wiley & Sons Ltd.
Keywords:
MHC, Tasmanian devil, Transmissible cancer, contagious cancer, immunopeptidome, marsupial
Identifiers
Local EPrints ID: 446666
URI: http://eprints.soton.ac.uk/id/eprint/446666
ISSN: 0019-2805
PURE UUID: 266f7331-a053-4c0e-a0dd-b4b44c36946a
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Date deposited: 17 Feb 2021 17:32
Last modified: 17 Mar 2024 03:34
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Contributors
Author:
A Gastaldello
Author:
S H Ramarathinam
Author:
A Bailey
Author:
R Owen
Author:
S Turner
Author:
A Kontouli
Author:
A W Purcell
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