Project description:The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum (ER), essential for establishing a hierarchical immune response. The PLC coordinates peptide translocation into the ER with loading and editing of major histocompatibility complex class I molecules (MHC-I). After final proofreading in the PLC, stable peptide/MHC-I complexes are released to the cell surface to evoke a T-cell response against infected or malignant cells. Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits into a single macromolecular assembly, including the transporter associated with antigen processing TAP1/2, the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin. The molecular organization and mechanistic events in the PLC are unknown due to the compositional heterogeneity and intrinsic dynamic nature of the complex. Here, PLC from Burkitt’s lymphoma cells was isolated using an engineered viral inhibitor as bait, followed by cross-linking mass spectrometry to aid EM structure elucidation.
Project description:Characterisation of peptide ligands of the Major histocompatibility class (MHC) I allele, HLA-B*57:01, expressed in the C1R (Class I reduced) B-lymphoblastoid cell line, after exposure to the anti-retroviral abacavir or abacavir analogues.
Project description:Characterisation of the kinetics of abacavir-induced perturbation of the immunopeptidome of the Major Histocompatibility Complex (MHC) class I molecule HLA-B*57:01.
Project description:Rhesus macaques vaccinated by rhesus cytomegalovirus vectors expressing simian immunodeficiency virus proteins (RhCMV/SIV) activate gene expression signature associated with IL15. To examine the gene expression signature activated by IL15, we performed longitudinal examinations of rhesus macaques during IL15 treament.
Project description:This SuperSeries is composed of the following subset Series: GSE33090: Dramatic effects of social behavior on gene regulation in rhesus macaques [Individual_expression] GSE34127: Dramatic effects of social behavior on gene regulation in rhesus macaques [Cell type_expression] GSE34128: Dramatic effects of social behavior on gene regulation in rhesus macaques [Bisulfite_seq] Refer to individual Series
Project description:Antler blastema progenitor cell (ABPC) is a novel type of skeletal mesenchymal stem cell with strong stemness and renewal ability. Here, we discovered that ABPC-derived extracellular vesicles (EVsABPCs) can strongly rejuvenate aging tissues in aged mice and rhesus macaques (Macaca mulattas). We identified a variety of rejuvenating molecules in EVsABPCs that differed from EVs of mouse bone marrow stromal stem cells (EVsBMSCs). EVsABPCs exhibited a robust in vitro ability to rejuvenate senescence BMSCs of aged mice and shift their molecular signature into a youthful state. In vivo, EVsABPCs increased bone mineral density in the femur by 2.4-fold in mice, and 1.53-fold in rhesus macaques. Besides, intravenous EVsABPCs significantly outperformed mouse fetal-EVsBMSCs in improving physical performance, reducing systemic inflammation, and rejuvenating major tissues of elderly mice, with no observed immunological side effects. Furthermore, EVsABPCs showed similar rejuvenating effects in old rhesus macaques as in elderly mice. Particularly, EVsABPCs resulted in remarkable improvements in brain structure and behaviors of elderly rhesus macaques, providing the first batch of evidence of EVs’ beneficial effects on aging brains in primates. These findings suggest that the ABPC is a novel and practical source of EVs containing a wealth of systemic rejuvenating factors and has considerable translational value for anti-aging interventions, particularly the rejuvenation of aging bones.
