Publications by authors named "Vivian Lindo"
Type 1 diabetes results from the destruction of pancreatic beta cells by autoreactive T cells. As an autoantigen with extremely high expression in beta cells, insulin triggers and sustains the autoimmune CD4 and CD8 T cell responses and islet inflammation. We have previously shown that deficiency for insulin-degrading enzyme (IDE), a ubiquitous cytosolic protease with very high affinity for insulin, induces endoplasmic reticulum (ER) stress and proliferation in islet cells and protects non-obese diabetic mice (NOD) from diabetes.
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- High-throughput screening in biopharmaceuticals cuts costs and speeds up drug development by enabling rapid selection of effective cell lines using small-scale cell culture systems like 24- and 96-deep-well plates.
- The study focuses on analyzing protein aggregation, a critical factor affecting drug safety and effectiveness, by integrating automated purification and aggregation evaluation of therapeutic proteins expressed in these plates.
- The new workflow allows for efficient screening of numerous clonal cell lines (384 in 32 hours) with minimal protein requirements, identifying and eliminating those with high aggregation levels early in the development process.
Monoclonal antibodies (mAbs) are extremely complex due to the presence of structural modifications resulting from enzymatic and chemical reactions such as glycosylation, glycation, deamidation, isomerisation, oxidation, aggregation and fragmentation. Size and charge variants analysis are carried out from the early stages of drug development throughout product lifetime to investigate product degradation pathways and optimise process conditions. However, conventional analytical workstreams for size and charge variant characterization are both time and sample demanding, requiring the application of multiple analytical methods.
View Article and Find Full Text PDFBioconjugates are an important class of therapeutic molecules. To date, glycan-based metabolic glycoengineering has had limited use in this field, due to the complexities of the endogenous glycosylation pathway and the lack of an glycosylation consensus sequence. Here, we describe the development of a versatile on-demand glycosylation system that uses a novel, widely applicable 5 amino acid glycosylation tag, and a metabolically engineered UDP-galactose-4-eperimase (GALE) knock-out cell line.
View Article and Find Full Text PDFBackground: Proteins are biomolecules that consist of sequences of amino acids (primary structure) which can further interact and cause the backbone to fold into more complex arrangements (secondary and tertiary structures). Any chemical alterations of the molecules after the translation of the messenger RNA code into a protein primary sequence are known as posttranslational modifications (PTMs). PTMs may affect the protein's functionality; thus it is necessary to identify them.
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- Major histocompatibility complex (MHC) class I molecules are crucial for presenting peptides to cytotoxic T lymphocytes, primarily derived from cellular protein degradation.
- The process of cross-presentation, particularly in dendritic cells, allows these cells to present peptides from internalized antigens, but the cellular mechanisms are not fully understood.
- This study identifies insulin-regulated aminopeptidase (IRAP) as a key player in cross-presentation, showing that IRAP's trimming of peptides in endosomal compartments is essential for this process, while not affecting the presentation of own cellular peptides.
Type 1 diabetes mellitus (T1DM) results from the destruction of beta cells by autoantigen-specific T cells. In the non-obese diabetic (NOD) mouse model, CD8+ T cells play an essential role in both the initial triggering of insulitis and its destructive phase, and proinsulin (PI) is one of the dominant target antigens (Ags). However, little is known about the beta cell epitopes presented by HLA class I molecules and recognized by human CD8+ T cells.
View Article and Find Full Text PDFType 1 diabetes is thought to result from the destruction of beta-cells by autoantigen-specific T-cells. Observations in the NOD mouse model suggest that CD8+ cytotoxic T-cells play an essential role in both the initial triggering of insulitis and its destructive phase. However, little is known about the epitopes derived from human beta-cell autoantigens and presented by HLA class I molecules.
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- - The endoplasmic reticulum in humans uses two aminopeptidases, ERAP1 and ERAP2, to trim HLA class I peptides, which is crucial for immune response.
- - ERAP1 was found to be less effective at removing certain N-terminal amino acids compared to ERAP2, indicating that both enzymes have distinct roles in peptide processing.
- - Both ERAP1 and ERAP2 work together for efficient trimming of longer peptides and are physically associated, functioning as a team to enhance antigen presentation in cells.