Expression of the Nonclassical MHC Class I, Saha-UD in the Transmissible Cancer Devil Facial Tumour Disease (DFTD).

Kathryn Hussey,Hannah V Siddle,Rodrigo Hamede,Alexandre Kreiss,Karsten Skjødt,Alison Caldwell,Ruth Pye,Gregory M Woods,Annalisa Gastaldello

doi:10.3390/pathogens11030351

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.

Highlights

Devil facial tumour disease (DFTD) is a transmissible cancer circulating in the Tasmanian devil (Sarcophilus harrisii), a marsupial species endemic to the Australian island of Tasmania [1]
IHC shows that DFTD tumours express Saha-UD, though expression varies between tumours
DFTD tumours are heterogeneous for Saha-UD expression, (Figure 2C) and, unexpectedly, we observe varied classical major histocompatibility complex class I (MHC-I) expression between tumours

Summary

Introduction

Devil facial tumour disease (DFTD) is a transmissible cancer circulating in the Tasmanian devil (Sarcophilus harrisii), a marsupial species endemic to the Australian island of Tasmania [1]. These tumour cells transmit as an allograft between devils due to biting behaviour during feeding and mating [2–4], forming new tumours on the face and/or neck of the new host. An immune response can be activated if the T cell recognises a nonself or mutated self peptide (for example, from a virus or cancer cell, respectively) or a nonself MHC-I heavy chain, such as in a transplant. Though devils have low genetic diversity at the MHC-I loci [15,16], it has been shown that devils are able to reject both

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Conclusion