Biology subjects

Curato, C.

Publications and source records attributed to Curato, C..

3 recordsLinked to original sources

bioRxiv2026

Identification of targetable epitope surfaces from the high resolution structure of the superantigen Staphylococcal Enterotoxin L

Emetic exotoxins secreted by Staphylococcus species (Staphylococcal enterotoxins, SEs) are a major cause of food poisoning cases worldwide and many are additionally classified as superantigens - able to potently activate T cells in an antigen independent manner. Fewer than half of the gene products of the known SE genes have been extensively characterized. The gene for Staphylococcal enterotoxin L (SEL) occurs in both foodborne and clinical isolates but no detailed structural characterization has yet been available. We report here the crystal structure of SEL and confirm its function as a superantigen via direct T cell activation assays. By comparison of the SEL sequence with that of its four closest homologues (SEI, SEK, SEM and SEQ), we have identified binding epitopes unique for SEL and mapped these regions onto the structure. These data provide the first high resolution view of SEL and the basis for the development of diagnostic procedures for its specific detection.

molecular biology↗

bioRxiv2019

{-}{-}{-}{-}{-}Polyglutamine-related aggregates serve as a potent antigen source for cross presentation by dendritic cells

Protective MHC-I dependent immune responses require an overlap between repertoires of proteins directly presented on target cells and cross-presented by professional antigen presenting cells (APC), specifically dendritic cells (DCs). How stable proteins that rely on DRiPs for direct presentation are captured for cell-to-cell transfer remains enigmatic. Here we address this issue using a combination of in vitro and in vivo approaches involving stable and unstable versions of ovalbumin model antigens displaying DRiP-dependent and -independent antigen presentation, respectively. Apoptosis, but not necrosis of donor cells was found associated with robust p62-dependent global protein aggregate formation and captured stable proteins permissive for DC cross-presentation. Potency of aggregates to serve as antigen source was directly demonstrated using polyglutamine-equipped model substrates. Collectively, our data implicate global protein aggregation in apoptotic cells as a mechanism that ensures the overlap between MHC-I epitopes presented directly or cross-presented by APC and demonstrate the unusual ability of DC to process stable protein aggregates.\n\nSummaryProtective T cell immunity relies on the overlap of the antigen repertoire expressed by cells and the repertoire presented by dendritic cells that are required to trigger naive T cells. We suggest a mechanism that contributes to ensure this antigenic overlap. Our findings demonstrate that upon apoptosis stable proteins are aggregated in p62-dependent pathway and that dendritic cells are capable to efficiently process these aggregates to retrieve antigens for T cell stimulation.

cell biology↗

bioRxiv2019

Defining Monocyte Differentiation into Colonic and Ileal Macrophages

Monocytes are circulating short-lived macrophage precursors that are recruited on demand from the blood to sites of inflammation and challenge. In steady state, classical monocytes give rise to vasculature-resident cells that patrol the luminal side of the endothelium. In addition, classical monocytes feed macrophage compartments of selected organs, including barrier tissues, such as the skin and intestine, as well as the heart. Monocyte differentiation under conditions of inflammation has been studied in considerable detail. In contrast, monocyte differentiation under non-inflammatory conditions remains less well understood. Here we took advantage of a combination of cell ablation and precursor engraftment to investigate the generation of gut macrophages from monocytes. Collectively, we identify factors associated with the gradual adaptation of monocytes to tissue residency. Moreover, comparison of monocyte differentiation into the colon and ileum-resident macrophages revealed the graduated acquisition of gut segment-specific gene expression signatures.

immunology↗