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Expression of the nonclassical MHC Class I, Saha-UD in the transmissible cancer devil facial tumour disease (DFTD)

Expression of the nonclassical MHC Class I, Saha-UD in the transmissible cancer devil facial tumour disease (DFTD)
Expression of the nonclassical MHC Class I, Saha-UD in the transmissible cancer devil facial tumour disease (DFTD)

Devil facial tumour disease (DFTD) is a transmissible cancer that has circulated in the Tasmanian devil population for >25 years. Like other contagious cancers in dogs and devils, the way DFTD escapes the immune response of its host is a central question to understanding this disease. DFTD has a low major histocompatibility complex class I (MHC-I) expression due to epigenetic modifications, preventing host immune recognition of mismatched MHC-I molecules by T cells. However, the total MHC-I loss should result in natural killer (NK) cell activation due to the ‘missing self’. Here, we have investigated the expression of the nonclassical MHC-I, Saha-UD as a potential regulatory or suppressive mechanism for DFTD. A monoclonal antibody was generated against the devil Saha-UD that binds recombinant Saha-UD by Western blot, with limited crossreactivity to the classical MHC-I, Saha-UC and nonclassical Saha-UK. Using this antibody, we confirmed the expression of Saha-UD in 13 DFTD tumours by immunohistochemistry (n = 15) and demonstrated that Saha-UD expression is heterogeneous, with 12 tumours showing intratumour heterogeneity. Immunohistochemical staining for the Saha-UD showed distinct patterns of expression when compared with classical MHC-I molecules. The nonclassical Saha-UD expression by DFTD tumours in vivo may be a mechanism for immunosuppression, and further work is ongoing to characterise its ligand on immune cells.

MHC class I, Tasmanian devils, immune evasion, nonclassical, transmissible cancer
2076-0817
Hussey, Kathryn
dadf026d-e958-4063-822d-23799466660d
Caldwell, Alison
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Kreiss, Alexandre
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Skjødt, Karsten
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Gastaldello, Annalisa
8b15e63b-94ed-4897-95c9-bc7fe2b37282
Pye, Ruth
d78c0147-beb8-4a5d-af46-5dfde24cd45a
Hamede, Rodrigo
b32b33c4-7cdd-40af-aa80-774ef48f822b
Woods, Gregory M.
5e97f157-aaa1-4e46-b718-c75bcf2fe611
Siddle, Hannah V.
2f0c1307-55d3-4965-a8b0-495c4a799f27
Hussey, Kathryn
dadf026d-e958-4063-822d-23799466660d
Caldwell, Alison
f431416a-765e-42a0-8516-c19c96035a2a
Kreiss, Alexandre
860c2193-1683-44ce-8809-0ac0c8cee2c5
Skjødt, Karsten
9692db3f-9512-4106-b006-6a312a3715f5
Gastaldello, Annalisa
8b15e63b-94ed-4897-95c9-bc7fe2b37282
Pye, Ruth
d78c0147-beb8-4a5d-af46-5dfde24cd45a
Hamede, Rodrigo
b32b33c4-7cdd-40af-aa80-774ef48f822b
Woods, Gregory M.
5e97f157-aaa1-4e46-b718-c75bcf2fe611
Siddle, Hannah V.
2f0c1307-55d3-4965-a8b0-495c4a799f27

Hussey, Kathryn, Caldwell, Alison, Kreiss, Alexandre, Skjødt, Karsten, Gastaldello, Annalisa, Pye, Ruth, Hamede, Rodrigo, Woods, Gregory M. and Siddle, Hannah V. (2022) Expression of the nonclassical MHC Class I, Saha-UD in the transmissible cancer devil facial tumour disease (DFTD). Pathogens, 11 (3), [351]. (doi:10.3390/pathogens11030351).

Record type: Article

Abstract

Devil facial tumour disease (DFTD) is a transmissible cancer that has circulated in the Tasmanian devil population for >25 years. Like other contagious cancers in dogs and devils, the way DFTD escapes the immune response of its host is a central question to understanding this disease. DFTD has a low major histocompatibility complex class I (MHC-I) expression due to epigenetic modifications, preventing host immune recognition of mismatched MHC-I molecules by T cells. However, the total MHC-I loss should result in natural killer (NK) cell activation due to the ‘missing self’. Here, we have investigated the expression of the nonclassical MHC-I, Saha-UD as a potential regulatory or suppressive mechanism for DFTD. A monoclonal antibody was generated against the devil Saha-UD that binds recombinant Saha-UD by Western blot, with limited crossreactivity to the classical MHC-I, Saha-UC and nonclassical Saha-UK. Using this antibody, we confirmed the expression of Saha-UD in 13 DFTD tumours by immunohistochemistry (n = 15) and demonstrated that Saha-UD expression is heterogeneous, with 12 tumours showing intratumour heterogeneity. Immunohistochemical staining for the Saha-UD showed distinct patterns of expression when compared with classical MHC-I molecules. The nonclassical Saha-UD expression by DFTD tumours in vivo may be a mechanism for immunosuppression, and further work is ongoing to characterise its ligand on immune cells.

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Accepted/In Press date: 4 March 2022
Published date: 14 March 2022
Additional Information: Funding Information: Funding: This work was funded by an Established Investigator grant from the Morris Animal Foundation to H.V.S. (D18ZO-104), the Australian Research Council (DP180100520) and funds raised by the Save the Tasmanian Devil Appeal; Wildcare Inc. by Saffire. K.H. and A.C. were funded by PhD scholarships from The Gerald Kerkut Charitable Trust and the University of Southampton. The Australian Research Council (DE170101116 and LP170101101) funded fieldwork and data collection for the study. Funding Information: This work was funded by an Established Investigator grant from the Morris Animal Foundation to H.V.S. (D18ZO-104), the Australian Research Council (DP180100520) and funds raised by the Save the Tasmanian Devil Appeal; Wildcare Inc. by Saffire. K.H. and A.C. were funded by PhD scholarships from The Gerald Kerkut Charitable Trust and the University of Southampton. The Australian Research Council (DE170101116 and LP170101101) funded fieldwork and data collection for the study. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
Keywords: MHC class I, Tasmanian devils, immune evasion, nonclassical, transmissible cancer
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Identifiers

Local EPrints ID: 472259
URI: http://eprints.soton.ac.uk/id/eprint/472259
DOI: doi:10.3390/pathogens11030351
ISSN: 2076-0817
PURE UUID: ffcc8683-4941-4b2d-827c-9a23ec53e1f3
ORCID for Kathryn Hussey: ORCID iD orcid.org/0000-0002-8882-1502
ORCID for Annalisa Gastaldello: ORCID iD orcid.org/0000-0002-4365-1191
ORCID for Hannah V. Siddle: ORCID iD orcid.org/0000-0003-2906-4385

Catalogue record

Date deposited: 30 Nov 2022 17:39
Last modified: 17 Mar 2024 03:58

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Contributors

Author: Kathryn Hussey ORCID iD
Author: Alison Caldwell
Author: Alexandre Kreiss
Author: Karsten Skjødt
Author: Annalisa Gastaldello ORCID iD
Author: Ruth Pye
Author: Rodrigo Hamede
Author: Gregory M. Woods
Author: Hannah V. Siddle ORCID iD

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