Figure 1. Mechanisms of immune evasion by DFTD cells. (A) Devil T lymphocytes fail to recognize devil facial tumor disease (DFTD) cells as the latter lack MHC molecules on their surface. This is mainly due to the deacetylation-dependent repression of transcription from β₂-microglobulin (β₂m), transporter associated with antigen presentation (TAP) 1 and TAP2-coding genes. In this situation, MHC Class I heavy chains are produced but retained in the endoplasmic reticulum (ER). Low levels of MHC Class I molecules may be found on the surface of DFTD cells owing to the synthesis of trace amounts of β₂m and to peptides derived from ER-resident proteins. (B) DFTD cells can re-express MHC Class I molecules on their surface. Upon interferon γ (IFNγ) treatment of DFTD cells, β₂m, TAP1, TAP2, MHC Class II molecules and the transcription factor Class II transactivator (CIITA) are upregulated and MHC Class I molecules are expressed on the cell surface. Devils vaccinated with MHC Class I-expressing DFTD cells are expected to activate a protective T-cell response. Insets represent magnified view of the ER.