Regulation of HLA-DR peptide occupancy by histone deacetylase inhibitors. 2013

Kevin Cronin, and Hernando Escobar, and Karoly Szekeres, and Eduardo Reyes-Vargas, and Alan L Rockwood, and Mark C Lloyd, and Julio C Delgado, and George Blanck
Department of Molecular Medicine; Morsani College of Medicine; University of South Florida; Tampa, FL USA.

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.

UI MeSH Term Description Entries
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006684 HLA-DR Antigens A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS. HLA-DR,Antigens, HLA-DR,HLA DR Antigens
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006877 Hydroxamic Acids A class of weak acids with the general formula R-CONHOH. Hydroxamic Acid,Acid, Hydroxamic,Acids, Hydroxamic
D000077337 Vorinostat A hydroxamic acid and anilide derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used in the treatment of CUTANEOUS T-CELL LYMPHOMA and SEZARY SYNDROME. 18F-SAHA,18F-Suberoylanilide Hydroxamic Acid,M344,MK-0683,MK0683,N-Hydroxy-N'-phenyloctanediamide,N1-Hydroxy-N8-phenyloctanediamide,NHNPODA,Suberanilohydroxamic Acid,Suberoyl Anilide Hydroxamic Acid,Suberoylanilide Hydroxamic Acid,Zolinza,18F Suberoylanilide Hydroxamic Acid,MK 0683,N Hydroxy N' phenyloctanediamide,N1 Hydroxy N8 phenyloctanediamide
D000944 Antigens, Differentiation, B-Lymphocyte Membrane antigens associated with maturation stages of B-lymphocytes, often expressed in tumors of B-cell origin. Antigens, Differentiation, B-Cell,B-Cell Differentiation Antigens,B-Lymphocyte Differentiation Antigens,Blast-2 Antigen, B-Cell,Differentiation Antigens, B-Cell,Differentiation Antigens, B-Lymphocyte,Leu Antigens, B-Lymphocyte,Plasma Cell Antigens PC-1,Antigens, Differentiation, B Lymphocyte,Antigens, Plasma Cell, PC-1,B-Cell Blast-2 Antigen,Antigen, B-Cell Blast-2,Antigens, B-Cell Differentiation,Antigens, B-Lymphocyte Differentiation,Antigens, B-Lymphocyte Leu,B Cell Blast 2 Antigen,B Cell Differentiation Antigens,B Lymphocyte Differentiation Antigens,B-Lymphocyte Leu Antigens,Blast 2 Antigen, B Cell,Differentiation Antigens, B Cell,Differentiation Antigens, B Lymphocyte,Leu Antigens, B Lymphocyte,Plasma Cell Antigens PC 1
D000949 Histocompatibility Antigens Class II Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen. Antigens, Immune Response,Class II Antigens,Class II Histocompatibility Antigen,Class II Major Histocompatibility Antigen,Ia Antigens,Ia-Like Antigen,Ia-Like Antigens,Immune Response Antigens,Immune-Associated Antigens,Immune-Response-Associated Antigens,MHC Class II Molecule,MHC II Peptide,Class II Antigen,Class II Histocompatibility Antigens,Class II MHC Proteins,Class II Major Histocompatibility Antigens,Class II Major Histocompatibility Molecules,I-A Antigen,I-A-Antigen,IA Antigen,MHC Class II Molecules,MHC II Peptides,MHC-II Molecules,Antigen, Class II,Antigen, I-A,Antigen, IA,Antigen, Ia-Like,Antigens, Class II,Antigens, Ia,Antigens, Ia-Like,Antigens, Immune-Associated,Antigens, Immune-Response-Associated,I A Antigen,II Peptide, MHC,Ia Like Antigen,Ia Like Antigens,Immune Associated Antigens,Immune Response Associated Antigens,MHC II Molecules,Molecules, MHC-II,Peptide, MHC II,Peptides, MHC II
D001402 B-Lymphocytes Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B-Cells, Lymphocyte,B-Lymphocyte,Bursa-Dependent Lymphocytes,B Cells, Lymphocyte,B Lymphocyte,B Lymphocytes,B-Cell, Lymphocyte,Bursa Dependent Lymphocytes,Bursa-Dependent Lymphocyte,Lymphocyte B-Cell,Lymphocyte B-Cells,Lymphocyte, Bursa-Dependent,Lymphocytes, Bursa-Dependent
D001549 Benzamides BENZOIC ACID amides.

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