We have now confirmed by testing NOD.IAPP−/− islet cells that expression of IAPP is critical for generation of the BDC-6.9 antigen. We have demonstrated that the precise epitope for the HIP-reactive BDC-6.9 clone is a region centered on the hybrid peptide junction between an insulin C-peptide fragment and IAPP2.

Then mini-mRNAs encoding these epitope sequences can be transfected into autologous antigen presenting cells (APCs), or the synthesized peptides can be loaded into autologous APCs and used to challenge purified peripheral T cells using the ELISPOT assay.

2023年10月9日 · Here, we describe a human monoclonal antibody selectively targeting IAPP oligomers and neutralizing IAPP aggregate toxicity by preventing membrane disruption and apoptosis in vitro.

2022年8月11日 · Increasing evidence suggested that the islet amyloid polypeptide (IAPP) is an essential autoantigen in the pathogenesis of type 1 diabetes (T1D) in humans and non-obese diabetic (NOD) mice. A unique disulfide containing IAPP-derived peptide KS20 is one of the highly diabetogenic peptides in NOD mice.

2013年6月11日 · In this report, we used a tag single nucleotide polymorphism (SNP) approach to select genetic variants of candidate genes (APCS, CPE, IAPP, IDE, PCSK1 and PCSK2) implicated in IAPP metabolism and tested their independent and joint associations with risk of T2D and beta cell dysfunction.

2021年8月29日 · Autoantigen expression in artificial APCs was driven by transgenes encoding human invariant chain (Ii 1-80)-β-cell autoantigen-BDC2.5 mimotope (HHPIWARMDA) fusions, or, in a transgene in which insulin (INS) and islet-amyloid polypeptide (IAPP) coding sequences were fused in-frame having their natural cleavage residues mutated to alanine.

2020年3月9日 · Here, we examined the immunopeptidome of the pancreatic islets in non-obese diabetic mice, which spontaneously develop autoimmune diabetes based on the I-A g7 variant of MHC-II. The relevant...

2021年7月14日 · The islet resident antigen-presenting cells (APCs) including dendritic cells and macrophages uptake and process the β cell-derived antigens to prime the autoreactive diabetogenic T cells. Upon activation, those autoreactive T cells produce copious amount of IFN-γ, TNF-α and IL-1β to induce β cell stress and death.

2024年8月29日 · A hybrid-insulin peptide (HIP) derived from insulin C-chain and ChgA (InsC-ChgA) was recently identified as the BDC-2.5 antigen. 6 In addition, CD4 + T cells specific for InsC-islet amyloid polypeptide (InsC-IAPP) HIP have been discovered within islets of mice 7; however, unlike responses to insulin and ChgA, IAPP deficiency fails to prevent ...

2024年12月24日 · APCS (Amyloid P Component, Serum) is a Protein Coding gene. Diseases associated with APCS include Candidiasis and Amyloidosis, Hereditary Systemic 2. Among its related pathways are Metabolism of proteins and RNA Polymerase I Promoter Opening.