期刊
HUMAN VACCINES & IMMUNOTHERAPEUTICS
卷 9, 期 4, 页码 784-789出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/hv.23085
关键词
histone deacetylase inhibitors; HLA-DR peptide occupancy; major histocompatibility class II; cathepsin; antigenic peptide
资金
- Department of Molecular Medicine at the Morsani College of Medicine
- ARUP Institute for Clinical and Experimental Pathology at the University of Utah
Numerous molecular effects have been attributed to histone deacetylase inhibitors (HDACI's), including the induction of major histocompatibility (MHC) genes. Here we report that one FDA approved HDACI, Vorinostat, and a second HDACI currently in clinical trials, Entinostat, reduce the ratio of class II associated invariant peptide (CLIP) to the MHC class II molecule, HLA-DR, indicating an increase in the non-CLIP peptides bound to HLA-DR. The HDACI effects are apparent with immortalized B-cells, HLA-DR constitutive melanoma cells and with melanoma cells expressing HLA-DR due to transformation with an expression vector for the HLA-DR gene co-activator, CIITA. Entinostat treatment leads to upregulation of Cathepsin L1, and the HLA-DR peptidome of the Entinostat treated cells is consistent with increased Cathepsin L1 mediated proteolysis. These results indicate that HDACI treatments may alter the HLA-DR peptidome of cells in patients and provide a way to identify novel immunogens for vaccinations and the study of autoantigens.
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