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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
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
0019-2805
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
53398b33-0596-4288-9647-69cff610e97c
Siddle, H V
2f0c1307-55d3-4965-a8b0-495c4a799f27
Gastaldello, A
8b15e63b-94ed-4897-95c9-bc7fe2b37282
Ramarathinam, S H
1c813383-c14c-44b1-8e7c-c34aa0cba1e8
Bailey, A
541e2cd9-ac72-4058-9293-def64fc2c284
Owen, R
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Turner, S
d689f03b-bc34-4533-8971-45fcbe3442c4
Kontouli, A
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Elliott, T
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Skipp, P
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Purcell, A W
53398b33-0596-4288-9647-69cff610e97c
Siddle, H V
2f0c1307-55d3-4965-a8b0-495c4a799f27

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), 169-184. (doi:10.1111/imm.13307).

Record type: Article

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.

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imm.13307 (1) - Version of Record
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Accepted/In Press date: 4 January 2021
e-pub ahead of print date: 18 January 2021
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
ORCID for A Gastaldello: ORCID iD orcid.org/0000-0002-4365-1191
ORCID for A Bailey: ORCID iD orcid.org/0000-0003-0023-8679
ORCID for T Elliott: ORCID iD orcid.org/0000-0003-1097-0222
ORCID for P Skipp: ORCID iD orcid.org/0000-0002-2995-2959

Catalogue record

Date deposited: 17 Feb 2021 17:32
Last modified: 26 Nov 2021 03:01

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Contributors

Author: A Gastaldello ORCID iD
Author: S H Ramarathinam
Author: A Bailey ORCID iD
Author: R Owen
Author: S Turner
Author: A Kontouli
Author: T Elliott ORCID iD
Author: P Skipp ORCID iD
Author: A W Purcell
Author: H V Siddle

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