H2-M and H2-O as Targeting Vehicles for the MHC Class II Processing Compartment Promote Antigen-Specific CD4+ T Cell Activation

CD8 and CD4 T cell activation are both required for a strong and long-lasting T cell immune response. Endogenously expressed proteins are readily processed by the MHC class I antigen presentation pathway, enabling activation of CD8+ T cells. However, the MHC class II antigen presentation pathway, necessary for CD4+ T cell activation, is generally not sufficiently accessible to endogenously expressed proteins, limiting the efficiency of mRNA- or DNA-based vaccines. In the current study, we have evaluated the feasibility of using antigen sequences fused to sequences derived from the H2-M and H2-O proteins, two complexes known to participate in MHC class II antigen processing, for the enhancement of CD4 T-cell activation. We analyzed T cell activation after genetic immunization with mRNA-encoding fusion proteins with the model antigen ovalbumin and sequences derived from H2-M or H2-O. Our results show that H2-M- or H2-O-derived sequences robustly improve antigen-specific CD4 T-cell activation when fused to the antigen of interest and suggest that the approach could be used to improve the efficiency of mRNA- or DNA-based vaccines.

Exploring Immune Infiltration and Biomarkers of Ollier Chondrosarcoma

BackgroundOllier disease (OD) is a kind of rare and non-hereditary orthopaedics disease. The malignancy transformation towards chondrosarcoma can cause catastrophic consequences. Our study aimed to reveal the potential molecule mechanism and hub genes involving in Ollier chondrosarcomas. The raw data GSE30835 was acquired from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between Ollier chondrosarcoma and healthy groups were identified. After Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs, protein-protein interaction (PPI) network construction, hub genes and significant modules were selected. CIBERSORT analysis was also carried out.ResultsTogether, 226 DEGs were identified, which contained 79 downregulated and 147 up-regulated. Functional and pathway enrichment analysis indicated that DEGs were mainly enriched in extracellular matrix (ECM) structural constituent, MHC class II antigen-related mechanism and phagosome pathway. Two significant modules were related to chondrocyte development, MHC class II antigen processing and presentation. COL3A1, VCAN, COL11A1, THBS1, ITGB1, CCL2, CCND1 were viewed as hub genes. CIBERSORT analysis shows that naive B cells and M0 macrophages are of statistical significance. ConclusionOur study suggests that COL3A1, COL11A1, VCAN, ITGB1, THBS1, CCL2, CCND1 may be viewed as promising candidate biomarkers of Ollier chondrosarcoma. We also advanced that MHC class II antigen-related immune mechanism should be paid attention in the further experiment. Naive B cells and M0 macrophages might be related to immune mechanism.

Effects of Colonization of Gnotobiotic Swiss Webster Mice with Helicobacter bilis

Helicobacter bilis (Hb) causes hepatitis in some strains of inbred mice. The current study confirmed that Hb directly causes portal hepatitis in outbred gnotobiotic Swiss Webster (SW) mice, as we previously reported for conventional SW mice. Hbmonoassociated SW mice also developed mild enterocolitis, expanded gut-associated lymphoid tissue (GALT), and tertiary lymphoid tissue in the lower bowel. At 1 and 10 mo after infection, Hb-induced GALT hyperplasia exhibited well-organized, ectopic germinal centers with increased mononuclear cell apoptosis, MHC class II antigen presentation, and pronounced endothelial venule formation, consistent with features of tertiary lymphoid tissue. In the lower bowel, Hb induced mainly B220+ cells as well as CD4+ IL17+, CD4+ IFNγ+, and CD4+ FoxP3+ regulatory T cells and significantly increased IL10 mRNA expression. This gnotobiotic model confirmed that Hb causes portal hepatitis in outbred SW mice but stimulated GALT with an antiinflammatory bias. Because Hb had both anti- and proinflammatory effects on GALT, it should be considered a 'pathosymbiont provocateur' and merits further evaluation in mouse models of human disease.