ABSTRACT: Identifying PD-1 interacting proteins in mouse CD4+ effector T cells expressing PD-1 at endogenous levels and after stimulation with pervanadate.
Project description:Identifying BTLA interacting proteins in mouse CD4+ effector T cells expressing BTLA at endogenous levels and after stimulation with pervanadate.
Project description:CD8+ T cells in chronic viral infections like HIV develop functional defects such as loss of IL-2 secretion and decreased proliferative potential that are collectively termed exhaustion1. Exhausted T cells express increased levels of multiple inhibitory receptors, such as Programmed Death 1 (PD-1). PD-1 inhibition contributes to impaired virus-specific T cell function in chronic infection because antibody-mediated blockade of its ligand, Programmed Death Ligand 1 (PD-L1) is sufficient to improve T cell function and reduce viral replication in animal models. Reversing PD-1 inhibition is therefore an attractive therapeutic target, but the cellular mechanisms by which PD-1 ligation results in T cell inhibition are not fully understood. PD-1 is thought to limit T cell activation by attenuating T cell receptor (TCR) signaling. It is not known whether PD-1 ligation also acts by upregulating genes in exhausted T cells that impair their function. Here, we analyzed gene-expression profiles from HIV-specific CD8+ T cells in patients with HIV and show that PD-1 coordinately upregulates a program of genes in exhausted CD8+ T cells from humans and mice. This program includes upregulation of basic leucine transcription factor, ATF-like (BATF), a transcription factor in the AP-1 family. Enforced expression of BATF was sufficient to impair T cell proliferation and cytokine secretion, while BATF knockdown reduced PD-1 inhibition. Silencing BATF in CD4+ and CD8+ T cells from chronic viremic patients rescued HIV-specific T cell function. Thus inhibitory receptors can cause T cell exhaustion by upregulating genes â such as BATF â that inhibit T cell function. PD-1 expressing Jurkat cells were cultured for 18 hours with beads coated with antibodies to CD3 and CD28, with our without an antibody to PD-1.
Project description:This SuperSeries is composed of the following subset Series: GSE40512: Gene expression profile of human T-ALL cell line KOPTK1 treated with vehicle or PD 0332991 GSE40513: Gene expression profile of mouse breast cancer V720 cells treated with vehicle or PD 0332991 Refer to individual Series
Project description:Parkinson's Disease (PD) and Non-Demented Control (NDC) human sera were probed onto human protein microarrays in order to identify differentially expressed autoantibody biomarkers that could be used as diagnostic indicators. In the study presented here, 29 PD and 40 NDC human serum samples were probed onto human protein microarrays in order to identify differentially expressed autoantibodies. Microarray data was analyzed using several statistical significance algorithms, and autoantibodies that demonstrated significant group prevelance were selected as biomarkers of disease. Prediction classification analysis tested the diagnostic efficacy of the identified biomarkers; and differentiation of PD samples from other neurodegeneratively-diseased and non-neurodegeneratively-diseased controls (Alzheimer's disease, multiple sclerosis, and breast cancer) confirmed their specificity.
Project description:SWATH analysis of Yeast Proteome over time in response to Osmotic Stress. We sampled cell cultures in biological triplicates at six time points following the application of osmotic stress and acquired single injection DIA datasets on a high-resolution 5600 tripleTOF instrument operated in SWATH mode. Proteins were quantified by the targeted extraction and signal integration from the SWATH-MS datasets of peak groups representing proteotypic peptides for specific yeast proteins.
Project description:Immune checkpoint inhibitors (ICIs) are a type of cancer treatment that work by targeting molecules on immune cells that can inhibit the immune system's ability to attack cancer cells. One such checkpoint molecule is PD-1, which is found on the surface of T cells (a type of immune cell) and helps to prevent them from attacking healthy cells. When PD-1 binds to its ligand (a molecule on the surface of some cells), it sends a signal to the T cell to \\"turn off\\" and not attack the cell. This mechanism is important in preventing the immune system from attacking healthy cells, but it can also be exploited by cancer cells to avoid detection and destruction by the immune system. In this study YUMM2.1 mouse tumour cells were implanted subcutaneously. The effect of IFN-γ-pre-treatment, PARP14 inhibition and PD-1 antibody treatment are reported by RNA-seq.