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

Autor: Kathryn Hussey, Alison Caldwell, Alexandre Kreiss, Karsten Skjødt, Annalisa Gastaldello, Ruth Pye, Rodrigo Hamede, Gregory M. Woods, Hannah V. Siddle
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Pathogens, Vol 11, Iss 3, p 351 (2022)
Druh dokumentu: article
ISSN: 2076-0817
DOI: 10.3390/pathogens11030351
Popis: 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.
Databáze: Directory of Open Access Journals