Biology subjects

Stamatakis, G.

Publications and source records attributed to Stamatakis, G..

4 recordsLinked to original sources

bioRxiv2022

A wide foodomics approach coupled with metagenomics elucidates the environmental signature of Protected Geographical Indication potatoes

The term "terroir" has been widely employed to link differential geographic phenotypes with sensorial signatures of agricultural food products, influenced by agricultural practices, soil type and climate. Nowadays, the Geographical Indications labeling has been developed to safeguard the quality of plant-derived food that is linked to a certain terroir and is generally considered as an indication of superior organoleptic properties and phytochemical profile. As the dynamics of agroecosystems are highly intricate, consisting of tangled networks of interactions between plants, microorganisms, and the surrounding environment, the recognition of the key molecular components of terroir fingerprinting remains a great challenge to protect both the origin and the safety of food commodities. Furthermore, the contribution of microbiome as a potential driver of the terroir signature has been underestimated until recently. Herein, we present a first comprehensive view of the multi-omic landscape related to transcriptome, proteome, epigenome, and metagenome of the popular Protected Geographical Indication potatoes of Naxos.

plant biology↗

bioRxiv2021

Allotypic variation in antigen processing controls antigenic peptide generation from SARS-CoV-2 S1 Spike Glycoprotein

Population genetic variability in immune system genes can often underlie variability in immune responses to pathogens. Cytotoxic T-lymphocytes are emerging as critical determinants of both SARS-CoV-2 infection severity and long-term immunity, either after recovery or vaccination. A hallmark of COVID-19 is its highly variable severity and breadth of immune responses between individuals. To address the underlying mechanisms behind this phenomenon we analyzed the proteolytic processing of S1 spike glycoprotein precursor antigenic peptides by 10 common allotypes of ER aminopeptidase 1 (ERAP1), a polymorphic intracellular enzyme that can regulate cytotoxic T-lymphocyte responses by generating or destroying antigenic peptides. We utilized a systematic proteomic approach that allows the concurrent analysis of hundreds of trimming reactions in parallel, thus better emulating antigen processing in the cell. While all ERAP1 allotypes were capable of producing optimal ligands for MHC class I molecules, including known SARS-CoV-2 epitopes, they presented significant differences in peptide sequences produced, suggesting allotype-dependent sequence biases. Allotype 10, previously suggested to be enzymatically deficient, was rather found to be functionally distinct from other allotypes. Our findings suggest that common ERAP1 allotypes can be a major source of heterogeneity in antigen processing and through this mechanism contribute to variable immune responses to COVID-19.

biochemistry↗

bioRxiv2020

Generation of SARS-CoV-2 S1 spike glycoprotein putative antigenic epitopes in vitro by intracellular aminopeptidases

Presentation of antigenic peptides by MHCI is central to cellular immune responses against viral pathogens. While adaptive immune responses versus SARS-CoV-2 can be of critical importance to both recovery and vaccine efficacy, how protein antigens from this pathogen are processed to generate antigenic peptides is largely unknown. Here, we analyzed the proteolytic processing of overlapping precursor peptides spanning the entire sequence of the S1 spike glycoprotein of SARS-CoV-2, by three key enzymes that generate antigenic peptides, aminopeptidases ERAP1, ERAP2 and IRAP. All enzymes generated shorter peptides with sequences suitable for binding onto HLA alleles, but with distinct specificity fingerprints. ERAP1 was the most efficient in generating peptides 8-11 residues long, the optimal length for HLA binding, while IRAP was the least efficient. The combination of ERAP1 with ERAP2 greatly limited the variability of peptide sequences produced. Less than 7% of computationally predicted epitopes were found to be produced experimentally, suggesting that aminopeptidase processing may constitute a significant filter to epitope presentation. These experimentally generated putative epitopes could be prioritized for SARS-CoV-2 immunogenicity studies and vaccine design. We furthermore propose that this in vitro trimming approach could constitute a general filtering method to enhance the prediction robustness for viral antigenic epitopes.

biochemistry↗

bioRxiv2019

Genetic deletion of Autotaxin from CD11b+ cells decreases the severity of experimental autoimmune encephalomyelitis

Autotaxin (ATX) is a secreted lysophospholipase D catalyzing the extracellular production of lysophosphatidic acid (LPA), a growth factor-like signaling lysophospholipid. ATX and LPA signaling have been incriminated in the pathogenesis of different chronic inflammatory diseases and various types of cancer. In this report, deregulated ATX and LPA levels were detected in the spinal cord and plasma of mice during the development of experimental autoimmune encephalomyelitis (EAE). Among the different sources of ATX expression in the inflamed spinal cord, F4/80+CD11b+ cells, mostly activated macrophages and microglia, were found to express ATX, further suggesting an autocrine role for ATX/LPA in their activation, an EAE hallmark. Accordingly, ATX genetic deletion from CD11b+ cells attenuated the severity of EAE, thus proposing a pathogenic role for the ATX/LPA axis in neuroinflammatory disorders.

immunology↗