SARS-CoV-2 mutations affect antigen processing by the proteasome to alter CD8+ T cell responses

Mutations within viral epitopes can result in escape from T cells, but the contribution of mutations in flanking regions of epitopes in SARS-CoV-2 has not been investigated. Focusing on two SARS-CoV-2 nucleoprotein CD8+ epitopes, we investigated the contribution of these flanking mutations to proteasomal processing and T cell activation. We found decreased NP9-17-B*27:05 CD8+ T cell responses to the NP-Q7K mutation, likely due to a lack of efficient epitope production by the proteasome, suggesting immune escape caused by this mutation. In contrast, NP-P6L and NP-D103 N/Y mutations flanking the NP9-17-B*27:05 and NP105-113-B*07:02 epitopes, respectively, increased CD8+ T cell responses associated with enhanced epitope production by the proteasome. Our results provide evidence that SARS-CoV-2 mutations outside the epitope could have a significant impact on proteasomal processing, either contributing to T cell escape or enhancement that may be exploited for future vaccine design

The application value of a new Zn(II) coordination polymer in the early diagnosis and treatment of infantile rickets

771-775In the present study, a new 1D Zn(II) coordination polymer (CP) on the basis of 2,5-bis(pyridine-2-yl)-1,3,4-thiadiazole (L) as linking ligand with the chemical formula of [ZnLCl2]n has been created via blending L with Zn salt (ZnCl2) and studied through single crystal X-ray diffraction and elemental analysis. Its application values on the early diagnosis and treatment of infantile rickets were determined and the relevant mechanism was studied in the meanwhile. Then, the QCT was used to measure the bone density of the infantile rickets animal after adding compound. Moreover, the activity of the wnt signaling routine in the bone tissue was assessed via real time RT-PCR. By investigating into the detail of the binding conformation from a molecular level, molecular docking simulation reveals that the expected biological activity of the Zn complex comes from the pyridine group

Autophagy-Dependent Generation of Free Fatty Acids Is Critical for Normal Neutrophil Differentiation

Neutrophils are critical and short-lived mediators of innate immunity that require constant replenishment. Their differentiation in the bone marrow requires extensive cytoplasmic and nuclear remodeling, but the processes governing these energy-consuming changes are unknown. While previous studies show that autophagy is required for differentiation of other blood cell lineages, its function during granulopoiesis has remained elusive. Here, we have shown that metabolism and autophagy are developmentally programmed and essential for neutrophil differentiation in vivo. Atg7-deficient neutrophil precursors had increased glycolytic activity but impaired mitochondrial respiration, decreased ATP production, and accumulated lipid droplets. Inhibiting autophagy-mediated lipid degradation or fatty acid oxidation alone was sufficient to cause defective differentiation, while administration of fatty acids or pyruvate for mitochondrial respiration rescued differentiation in autophagy-deficient neutrophil precursors. Together, we show that autophagy-mediated lipolysis provides free fatty acids to support a mitochondrial respiration pathway essential to neutrophil differentiation