scholarly journals Generation of MHC class I diversity in primary tumors and selection of the malignant phenotype

2014 ◽  
Vol 138 (2) ◽  
pp. 271-280 ◽  
Author(s):  
Federico Garrido ◽  
Irene Romero ◽  
Natalia Aptsiauri ◽  
Angel M. Garcia-Lora
Keyword(s):  
Mhc Class I ◽  
Class I ◽  
Malignant Phenotype ◽  
Primary Tumors ◽  
Selection Of

scholarly journals Selection of Substrates for MHC Class I‐Restricted Antigen Processing

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Laurence Crane Eisenlohr ◽  
Lan Huang ◽  
Kerstin Kandler ◽  
Matthew Kuhls
Keyword(s):  
Mhc Class I ◽  
Antigen Processing ◽  
Class I ◽  
Selection Of

scholarly journals Reduced chromatin binding of MYC is a key effect of HDAC inhibition in MYC amplified medulloblastoma

2020 ◽  
Author(s):  
Jonas Ecker ◽  
Venu Thatikonda ◽  
Gianluca Sigismondo ◽  
Florian Selt ◽  
Gintvile Valinciute ◽  
...  
Keyword(s):  
Molecular Interaction ◽  
Hdac Inhibitors ◽  
Class I ◽  
Chromatin Binding ◽  
Hdac Inhibition ◽  
Primary Tumors ◽  
Chip Sequencing ◽  
Class I Hdacs ◽  
The Impact ◽  
Selection Of

Abstract Background The sensitivity of myelocytomatosis oncogene (MYC) amplified medulloblastoma to class I histone deacetylase (HDAC) inhibition has been shown previously; however, understanding the underlying molecular mechanism is crucial for selection of effective HDAC inhibitors for clinical use. The aim of this study was to investigate the direct molecular interaction of MYC and class I HDAC2, and the impact of class I HDAC inhibition on MYC function. Methods Co-immunoprecipitation and mass spectrometry were used to determine the co-localization of MYC and HDAC2. Chromatin immunoprecipitation (ChIP) sequencing and gene expression profiling were used to analyze the co-localization of MYC and HDAC2 on DNA and the impact on transcriptional activity in primary tumors and a MYC amplified cell line treated with the class I HDAC inhibitor entinostat. The effect on MYC was investigated by quantitative real-time PCR, western blot, and immunofluorescence. Results HDAC2 is a cofactor of MYC in MYC amplified medulloblastoma. The MYC-HDAC2 complex is bound to genes defining the MYC-dependent transcriptional profile. Class I HDAC inhibition leads to stabilization and reduced DNA binding of MYC protein, inducing a downregulation of MYC activated genes (MAGs) and upregulation of MYC repressed genes (MRGs). MAGs and MRGs are characterized by opposing biological functions and by distinct enhancer-box distribution. Conclusions Our data elucidate the molecular interaction of MYC and HDAC2 and support a model in which inhibition of class I HDACs directly targets MYC’s transactivating and transrepressing functions.

scholarly journals Increase in positive selection of CD8+ T cells in TAP1-mutant mice by human beta 2-microglobulin transgene.

1995 ◽  
Vol 181 (2) ◽  
pp. 787-792 ◽  
Author(s):  
H Martien van Santen ◽  
A Woolsey ◽  
P G Rickardt ◽  
L Van Kaer ◽  
E J Baas ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Surface ◽  
Mhc Class I ◽  
Cd8 T Cells ◽  
Surface Expression ◽  
Class I ◽  
Cell Surface Expression ◽  
Beta 2 ◽  
Beta 2 Microglobulin ◽  
Selection Of

Mice harboring a deletion of the gene encoding the transporter associated with antigen presentation-1 (TAP1) are impaired in providing major histocompatibility complex (MHC) class I molecules with peptides of cytosolic origin and lack stable MHC class I cell surface expression. They consequently have a strongly reduced number of CD8+ T cells. To examine whether selection of CD8+ T cells is dependent on TAP-dependent peptides, we partially restored MHC class I cell surface expression in TAP1-deficient mice by introduction of human beta 2-microglobulin. We show that selection of functional CD8+ T cells can be augmented in vivo in the absence of TAP1-dependent peptides.

Preferential binding of unusually long peptides to MHC class I and its influence on the selection of target peptides for T cell recognition

2008 ◽  
Vol 45 (6) ◽  
pp. 1818-1824 ◽  
Author(s):  
Jacqueline M. Burrows ◽  
Melissa J. Bell ◽  
Rebekah Brennan ◽  
John J. Miles ◽  
Rajiv Khanna ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
Class I ◽  
Cell Recognition ◽  
T Cell Recognition ◽  
Preferential Binding ◽  
Selection Of

scholarly journals Requirement for CD8-major histocompatibility complex class I interaction in positive and negative selection of developing T cells.

1992 ◽  
Vol 176 (1) ◽  
pp. 89-97 ◽  
Author(s):  
N Killeen ◽  
A Moriarty ◽  
H S Teh ◽  
D R Littman
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class I ◽  
Negative Selection ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecules ◽  
Selection Of

The interaction of the T cell surface glycoprotein CD8 with major histocompatibility complex (MHC) class I molecules on target cells is required for effective T cell activation. Mutations in the alpha 3 domain of the MHC class I molecule can disrupt binding to CD8, yet leave antigen presentation unaffected. Here we show that such a mutation can interfere with positive and negative selection of T cells bearing T cell receptors (TCRs) that interact specifically with the mutant class I molecule. Autoreactive T cells in male mice expressing a transgenic TCR specific for the male antigen H-Y and H-2Db were not deleted in the context of a transgenic Db molecule bearing a mutation at residue 227. Similarly, CD8+ cells were not positively selected in female mice expressing both the TCR and mutant class I transgenes. Endogenous MHC class I molecules were competent to bind CD8, but were unable to rescue the defect, indicating a requirement for coordinate recognition of antigen/MHC by a complex of the TCR and CD8 coreceptor for both positive and negative selection of thymocytes.

scholarly journals Potential Target Antigens for a Universal Vaccine in Epithelial Ovarian Cancer

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Renee Vermeij ◽  
Toos Daemen ◽  
Geertruida H. de Bock ◽  
Pauline de Graeff ◽  
Ninke Leffers ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Mhc Class I ◽  
Tumor Antigens ◽  
Therapeutic Vaccine ◽  
Class I ◽  
Vaccine Strategy ◽  
Universal Vaccine ◽  
Primary Tumors ◽  
Microarray Expression

The prognosis of epithelial ovarian cancer (EOC), the primary cause of death from gynaecological malignancies, has only modestly improved over the last decades. Immunotherapeutic treatment using a cocktail of antigens has been proposed as a “universal” vaccine strategy. We determined the expression of tumor antigens in the context of MHC class I expression in 270 primary tumor samples using tissue microarray. Expression of tumor antigens p53, SP17, survivin, WT1, and NY-ESO-1 was observed in 120 (48.0%), 173 (68.9%), 208 (90.0%), 129 (56.3%), and 27 (11.0%) of 270 tumor specimens, respectively. In 93.2% of EOC, at least one of the investigated tumor antigens was (over)expressed. Expression of MHC class I was observed in 78.1% of EOC. In 3 out 4 primary tumors, (over)expression of a tumor antigen combined with MHC class I was observed. These results indicate that a multiepitope vaccine, comprising these antigens, could serve as a universal therapeutic vaccine for the vast majority of ovarian cancer patients.

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