Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Supramolecular Peptide Nanofibers Engage Mechanisms of Autophagy in Antigen-Presenting Cells.

ABSTRACT: Supramolecular peptide nanofibers are attractive for applications in vaccine development due to their ability to induce strong immune responses without added adjuvants or associated inflammation. Here, we report that self-assembling peptide nanofibers bearing CD4+ or CD8+ T cell epitopes are processed through mechanisms of autophagy in antigen-presenting cells (APCs). Using standard in vitro antigen presentation assays, we confirmed loss and gain of the adjuvant function using pharmacological modulators of autophagy and APCs deficient in multiple autophagy proteins. The incorporation of microtubule-associated protein 1A/1B-light chain-3 (LC3-II) into the autophagosomal membrane, a key biological marker for autophagy, was confirmed using microscopy. Our findings indicate that autophagy in APCs plays an essential role in the mechanism of adjuvant action of supramolecular peptide nanofibers.

SUBMITTER: Rudra JS

PROVIDER: S-EPMC5748271 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Biomimetic strategy for cartilage formation: synergy of stem cell micro-aggregates and supramolecular peptide nanofibers

Project description:Recapitulation of embryonic developmental events is receiving increasing recognition as a strategy to induce robust tissue regeneration. In this work, we aimed to explore the critical events of cartilage formation by combining adult human bone marrow-derived mesenchymal stromal cells (hBMSCs) with supramolecular nanofibrous hydrogel. The micro-aggregation led to the altered global transcriptional profiles of hBMSCs and enhanced chondrogenic commitment early in 24h. Furthermore, the supramolecular nanofiber structure formed by peptide amphiphiles (PAs) maintained the cell cohesion and favored the deposition of cartilaginous matrix, thus facilitating the progression of differentiation. Upon subcutaneous implantation, the hBMSCs microaggregates-laden PA hydrogel demonstrated evident ectopic cartilage formation. Notably, RNA-sequencing data illustrated that the PA hydrogel facilitated the in vivo chondrogenesis progression of the encapsulated donor cells, and also activated the chondrogenesis in the host tissue via paracrine signaling. We conclude that PA hydrogel delivering microaggregates of hBMSCs could recapitulate the critical developmental events during cartilage development. This bioinspired approach will offer the potential to regenerate functional and durable tissues for the functional recovery of traumatic injuries of the cartilaginous skeleton .

2022-12-21 | GSE133727 | GEO

A Supramolecular Vaccine Platform Based on α-Helical Peptide Nanofibers.

Project description:A supramolecular peptide vaccine system was designed in which epitope-bearing peptides self-assemble into elongated nanofibers composed almost entirely of alpha-helical structure. The nanofibers were readily internalized by antigen presenting cells and produced robust antibody, CD4+ T-cell, and CD8+ T-cell responses without supplemental adjuvants in mice. Epitopes studied included a cancer B-cell epitope from the epidermal growth factor receptor class III variant (EGFRvIII), the universal CD4+ T-cell epitope PADRE, and the model CD8+ T-cell epitope SIINFEKL, each of which could be incorporated into supramolecular multi-epitope nanofibers in a modular fashion.

| S-EPMC6364304 | biostudies-literature

Multiepitope supramolecular peptide nanofibers eliciting coordinated humoral and cellular antitumor immune responses.

Project description:Subunit vaccines inducing antibodies against tumor-specific antigens have yet to be clinically successful. Here, we use a supramolecular α-helical peptide nanofiber approach to design epitope-specific vaccines raising simultaneous B cell, CD8+ T cell, and CD4+ T cell responses against combinations of selected epitopes and show that the concurrent induction of these responses generates strong antitumor effects in mice, with significant improvements over antibody or CD8+ T cell-based vaccines alone, in both prophylactic and therapeutic subcutaneous melanoma models. Nanofiber vaccine-induced antibodies mediated in vitro tumoricidal antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). The addition of immune checkpoint and phagocytosis checkpoint blockade antibodies further improved the therapeutic effect of the nanofiber vaccines against murine melanoma. These findings highlight the potential clinical benefit of vaccine-induced antibody responses for tumor treatments, provided that they are accompanied by simultaneous CD8+ and CD4+ responses, and they illustrate a multiepitope cancer vaccine design approach using supramolecular nanomaterials.

| S-EPMC9299545 | biostudies-literature

Single cell force spectroscopy of T cells recognizing a myelin-derived peptide on antigen presenting cells.

Project description:T-cell recognition of peptide-MHC complexes on APCs requires cell-cell interactions. The molecular events leading to T-cell activation have been extensively investigated, but the underlying physical binding forces between T-cells and APCs are largely unknown. We used single cell force spectroscopy for quantitation of interaction forces between T-cells and APCs presenting a tolerogenic peptide derived from myelin basic protein. When T-cells were brought into contact with peptide-loaded APCs, interaction forces increased with time from about 0.5nN after 10s interaction to about 15nN after 30min. In the absence of antigen, or when ICAM-1-negative APC was used, no increase in binding forces was observed. The temporal development of interaction forces correlated with the kinetics of immune synapse formation, as determined by LFA-1 and TCR enrichment at the interface of T-cell/APC conjugates using high throughput multispectral imaging flow cytometry. Together, these results suggest that ICAM-1/LFA-1 redistribution to the contact area is mainly responsible for development of strong interaction forces. High forces will keep T-cells and APCs in tight contact, thereby providing a platform for optimal interaction between TCRs and peptide-MHC complexes.

| S-EPMC3821867 | biostudies-literature

MHC class I antigen cross-presentation mediated by PapMV nanoparticles in human antigen-presenting cells is dependent on autophagy.

Project description:Nanoparticles made of the coat protein of papaya mosaic virus (PapMV) and a single-strand RNA were previously shown to be an efficient antigen presentation system for the trigger of cellular immunity. Engineering of PapMV nano with a cytotoxic T lymphocyte epitope was previously shown activating specific T lymphocytes through a proteasome-independent major histocompatibility complex class I (MHC-I) cross-presentation. In this study, we provide new insights into the mechanism of the MHC-I cross-presentation mediated by PapMV nanoparticles. We demonstrate that PapMV nanoparticles do not require the transporter associated with antigen presentation (TAP), but rather depend on lysosome acidification and cathepsin S protease activity for presentation of the T cell epitope. We have also linked the induction of autophagy with this vacuolar MHC-I cross-presentation process. Interestingly, autophagy is induced in antigen-presenting cells after PapMV nanoparticles exposure and inhibition of autophagy reduce MHC-I cross-presentation. This study demonstrates that autophagy is associated with TAP- and proteasome-independent MHC-I cross-presentation. A deeper understanding of the autophagy-dependent MHC-I cross-presentation will be useful in designing vaccination platforms that aim to trigger an efficient cytotoxic T lymphocyte response.

| S-EPMC8719699 | biostudies-literature

Antigen Presenting Dendritic Cells

Project description:Assessing the gene expression repertoire of antigen presenting dendritic cells Keywords: other

2004-09-30 | GSE702 | GEO

Supramolecular One-Dimensional n/p-Nanofibers.

Project description:Currently, there is a broad interest in the control over creating ordered electroactive nanostructures, in which electron donors and acceptors are organized at similar length scales. In this article, a simple and efficient procedure is reported en-route towards the construction of 1D arrays of crystalline pristine C60 and phenyl-C61-butyric acid methyl ester (PCBM) coated onto supramolecular fibers based on exTTF-pentapeptides. The resulting n/p-nanohybrids have been fully characterized by a variety of spectroscopic (FTIR, UV-Vis, circular dichroism, Raman and transient absorption), microscopic (AFM, TEM, and SEM), and powder diffraction (X-ray) techniques. Our experimental findings document the tendency of electroactive exTTF-fibers to induce the crystallization of C60 and PCBM, on one hand, and to afford 1D n/p-nanohybrids, on the other hand. Furthermore, photogenerated radical ion pairs, formed upon visible light irradiation of the n/p-nanohybrids, feature lifetimes on the range of 0.9-1.2 ns.

| S-EPMC5378913 | biostudies-literature

Supramolecular nanofibers and hydrogels of nucleopeptides.

Project description: Not available

| S-EPMC3251214 | biostudies-literature

HIV envelope antigen valency on peptide nanofibers modulates antibody magnitude and binding breadth.

Project description:A major challenge in developing an effective vaccine against HIV-1 is the genetic diversity of its viral envelope. Because of the broad range of sequences exhibited by HIV-1 strains, protective antibodies must be able to bind and neutralize a widely mutated viral envelope protein. No vaccine has yet been designed which induces broadly neutralizing or protective immune responses against HIV in humans. Nanomaterial-based vaccines have shown the ability to generate antibody and cellular immune responses of increased breadth and neutralization potency. Thus, we have developed supramolecular nanofiber-based immunogens bearing the HIV gp120 envelope glycoprotein. These immunogens generated antibody responses that had increased magnitude and binding breadth compared to soluble gp120. By varying gp120 density on nanofibers, we determined that increased antigen valency was associated with increased antibody magnitude and germinal center responses. This study presents a proof-of-concept for a nanofiber vaccine platform generating broad, high binding antibody responses against the HIV-1 envelope glycoprotein.

| S-EPMC8280189 | biostudies-literature

Antigen-presenting innate lymphoid cells orchestrate neuroinflammation.

Project description:Pro-inflammatory T cells in the central nervous system (CNS) are causally associated with multiple demyelinating and neurodegenerative diseases1-6, but the pathways that control these responses remain unclear. Here we define a population of inflammatory group 3 innate lymphoid cells (ILC3s) that infiltrate the CNS in a mouse model of multiple sclerosis. These ILC3s are derived from the circulation, localize in proximity to infiltrating T cells in the CNS, function as antigen-presenting cells that restimulate myelin-specific T cells, and are increased in individuals with multiple sclerosis. Notably, antigen presentation by inflammatory ILC3s is required to promote T cell responses in the CNS and the development of multiple-sclerosis-like disease in mouse models. By contrast, conventional and tissue-resident ILC3s in the periphery do not appear to contribute to disease induction, but instead limit autoimmune T cell responses and prevent multiple-sclerosis-like disease when experimentally targeted to present myelin antigen. Collectively, our data define a population of inflammatory ILC3s that is essential for directly promoting T-cell-dependent neuroinflammation in the CNS and reveal the potential of harnessing peripheral tissue-resident ILC3s for the prevention of autoimmune disease.

| S-EPMC8702489 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data