{"entity": "researcher", "timestamp": "2026-08-20T21:10:16.643Z", "family": "Ricagno", "given": "Stefano", "initials": "S", "orcid": "0000-0001-6678-5873", "affiliations": ["Dipartimento di Bioscienze, Universit\u00e0 degli Studi di Milano, Milano 20133, Italy.", "Institute of Molecular and Translational Cardiology, IRCCS Policlinico San Donato, San Donato Milanese 20097, Italy."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/98daac35c7914d1584403a45a81bd8c4.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/98daac35c7914d1584403a45a81bd8c4"}}, "publications": [{"entity": "publication", "iuid": "e550290a61734c6b853bf5c6b7a68db5", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e550290a61734c6b853bf5c6b7a68db5.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e550290a61734c6b853bf5c6b7a68db5"}}, "title": "l- to d-Amino Acid Substitution in the Immunodominant LCMV-Derived Epitope gp33 Highlights the Sensitivity of the TCR Recognition Mechanism for the MHC/Peptide Structure and Dynamics.", "authors": [{"family": "Ballabio", "given": "Federico", "initials": "F"}, {"family": "Broggini", "given": "Luca", "initials": "L"}, {"family": "Paissoni", "given": "Cristina", "initials": "C"}, {"family": "Han", "given": "Xiao", "initials": "X"}, {"family": "Peqini", "given": "Kaliroi", "initials": "K"}, {"family": "Sala", "given": "Benedetta Maria", "initials": "BM"}, {"family": "Sun", "given": "Renhua", "initials": "R"}, {"family": "Sandalova", "given": "Tatyana", "initials": "T"}, {"family": "Barbiroli", "given": "Alberto", "initials": "A", "orcid": "0000-0003-1678-5431", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cc60100306cf465b90ef3f261da249c0.json"}}, {"family": "Achour", "given": "Adnane", "initials": "A"}, {"family": "Pellegrino", "given": "Sara", "initials": "S", "orcid": "0000-0002-2325-3583", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c0d6ed24c4914ce4b6cd0f699f121b52.json"}}, {"family": "Ricagno", "given": "Stefano", "initials": "S", "orcid": "0000-0001-6678-5873", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/98daac35c7914d1584403a45a81bd8c4.json"}}, {"family": "Camilloni", "given": "Carlo", "initials": "C", "orcid": "0000-0002-9923-8590", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a695085d37ed428f8994e55f5b7ccc8d.json"}}], "type": "journal article", "published": "2022-03-22", "journal": {"title": "ACS Omega", "issn": "2470-1343", "volume": "7", "issue": "11", "pages": "9622-9635", "issn-l": "2470-1343"}, "abstract": "Presentation of pathogen-derived epitopes by major histocompatibility complex I (MHC-I) can lead to the activation and expansion of specific CD8+ T cell clones, eventually resulting in the destruction of infected target cells. Altered peptide ligands (APLs), designed to elicit immunogenicity toward a wild-type peptide, may affect the overall stability of MHC-I/peptide (pMHC) complexes and modulate the recognition by T cell receptors (TCR). Previous works have demonstrated that proline substitution at position 3 (p3P) of different MHC-restricted epitopes, including the immunodominant LCMV-derived epitope gp33 and escape variants, may be an effective design strategy to increase epitope immunogenicity. These studies hypothesized that the p3P substitution increases peptide rigidity, facilitating TCR binding. Here, molecular dynamics simulations indicate that the p3P modification rigidifies the APLs in solution predisposing them for the MHC-I loading as well as once bound to H-2Db, predisposing them for TCR binding. Our results also indicate that peptide position 6, key for interaction of H-2Db/gp33 with the TCR P14, takes a suboptimal conformation before as well as after binding to the TCR. Analyses of H-2Db in complex with APLs, in which position 6 was subjected to an l- to d-amino acid modification, revealed small conformational changes and comparable pMHC thermal stability. However, the l- to d-modification reduced significantly the binding to P14 even in the presence of the p3P modification. Our combined data highlight the sensitivity of the TCR for the conformational dynamics of pMHC and provide further tools to dissect and modulate TCR binding and immunogenicity via APLs.", "doi": "10.1021/acsomega.1c06964", "pmid": "35350306", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8945122"}], "notes": [], "created": "2026-08-20T08:12:34.879Z", "modified": "2026-08-20T08:12:35.056Z"}, {"entity": "publication", "iuid": "dd40d066b1144abd916ce6b8b0404f0f", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/dd40d066b1144abd916ce6b8b0404f0f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/dd40d066b1144abd916ce6b8b0404f0f"}}, "title": "Glycosylation Tunes Neuroserpin Physiological and Pathological Properties.", "authors": [{"family": "Visentin", "given": "Cristina", "initials": "C"}, {"family": "Broggini", "given": "Luca", "initials": "L", "orcid": "0000-0001-9472-6854", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6d44323acec54f35bc1dfa9a7fe3b32d.json"}}, {"family": "Sala", "given": "Benedetta Maria", "initials": "BM", "orcid": "0000-0002-1592-0817", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f03e2bb1aeba4436a2f1571f50335b87.json"}}, {"family": "Russo", "given": "Rosaria", "initials": "R"}, {"family": "Barbiroli", "given": "Alberto", "initials": "A"}, {"family": "Santambrogio", "given": "Carlo", "initials": "C", "orcid": "0000-0003-3986-6971", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/646bc8daee924c01a486497b0c2c7784.json"}}, {"family": "Nonnis", "given": "Simona", "initials": "S", "orcid": "0000-0002-3453-7282", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3d6cdb1b649c45ec9b4743996c5ac04f.json"}}, {"family": "Dubnovitsky", "given": "Anatoly", "initials": "A", "orcid": "0000-0002-5350-4531", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c926583bfad245bcb084a2a5409f25c0.json"}}, {"family": "Bolognesi", "given": "Martino", "initials": "M", "orcid": "0000-0002-9253-5170", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/58bd69e6035a4838863b772f3140b442.json"}}, {"family": "Miranda", "given": "Elena", "initials": "E", "orcid": "0000-0002-0586-8795", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5f1a54969560477b8df9bc2612bd3aaa.json"}}, {"family": "Achour", "given": "Adnane", "initials": "A"}, {"family": "Ricagno", "given": "Stefano", "initials": "S", "orcid": "0000-0001-6678-5873", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/98daac35c7914d1584403a45a81bd8c4.json"}}], "type": "journal article", "published": "2020-05-03", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "21", "issue": "9", "issn-l": null}, "abstract": "Neuroserpin (NS) is a member of the serine protease inhibitors superfamily. Specific point mutations are responsible for its accumulation in the endoplasmic reticulum of neurons that leads to a pathological condition named familial encephalopathy with neuroserpin inclusion bodies (FENIB). Wild-type NS presents two N-glycosylation chains and does not form polymers in vivo, while non-glycosylated NS causes aberrant polymer accumulation in cell models. To date, all in vitro studies have been conducted on bacterially expressed NS, de facto neglecting the role of glycosylation in the biochemical properties of NS. Here, we report the expression and purification of human glycosylated NS (gNS) using a novel eukaryotic expression system, LEXSY. Our results confirm the correct N-glycosylation of wild-type gNS. The fold and stability of gNS are not altered compared to bacterially expressed NS, as demonstrated by the circular dichroism and intrinsic tryptophan fluorescence assays. Intriguingly, gNS displays a remarkably reduced polymerisation propensity compared to non-glycosylated NS, in keeping with what was previously observed for wild-type NS in vivo and in cell models. Thus, our results support the relevance of gNS as a new in vitro tool to study the molecular bases of FENIB.", "doi": "10.3390/ijms21093235", "pmid": "32375228", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7247563"}, {"db": "pii", "key": "ijms21093235"}], "notes": [], "created": "2026-08-20T13:41:11.395Z", "modified": "2026-08-20T13:41:11.697Z"}, {"entity": "publication", "iuid": "050fbe86e588405eaa7d3cf8729266bf", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/050fbe86e588405eaa7d3cf8729266bf.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/050fbe86e588405eaa7d3cf8729266bf"}}, "title": "Biochemical and biophysical comparison of human and mouse beta-2 microglobulin reveals the molecular determinants of low amyloid propensity.", "authors": [{"family": "Achour", "given": "Adnane", "initials": "A"}, {"family": "Broggini", "given": "Luca", "initials": "L"}, {"family": "Han", "given": "Xiao", "initials": "X"}, {"family": "Sun", "given": "Renhua", "initials": "R", "orcid": "0000-0002-8203-4946", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/29b44e08db3a4482a6a40bbda52fe815.json"}}, {"family": "Santambrogio", "given": "Carlo", "initials": "C"}, {"family": "Buratto", "given": "Jeremie", "initials": "J"}, {"family": "Visentin", "given": "Cristina", "initials": "C"}, {"family": "Barbiroli", "given": "Alberto", "initials": "A"}, {"family": "De Luca", "given": "Chiara Maria Giulia", "initials": "CMG"}, {"family": "Sormanni", "given": "Pietro", "initials": "P"}, {"family": "Moda", "given": "Fabio", "initials": "F"}, {"family": "De Simone", "given": "Alfonso", "initials": "A"}, {"family": "Sandalova", "given": "Tatyana", "initials": "T"}, {"family": "Grandori", "given": "Rita", "initials": "R"}, {"family": "Camilloni", "given": "Carlo", "initials": "C"}, {"family": "Ricagno", "given": "Stefano", "initials": "S", "orcid": "0000-0001-6678-5873", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/98daac35c7914d1584403a45a81bd8c4.json"}}], "type": "journal article", "published": "2020-02-00", "journal": {"title": "FEBS J.", "issn": "1742-4658", "volume": "287", "issue": "3", "pages": "546-560", "issn-l": "1742-464X"}, "abstract": "The molecular bases of amyloid aggregation propensity are still poorly understood, especially for proteins that display a stable folded native structure. A prototypic example is human beta-2 microglobulin (\u03b22m), which, when accumulated in patients, gives rise to dialysis-related amyloidosis. Interestingly, although the physiologic concentration of \u03b22m in mice is five times higher than that found in human patients, no amyloid deposits are observed in mice. Moreover, murine \u03b22m (m\u03b22m) not only displays a lower amyloid propensity both in vivo and in vitro but also inhibits the aggregation of human \u03b22m in vitro. Here, we compared human and m\u03b22m for their aggregation propensity, ability to form soluble oligomers, stability, three-dimensional structure and dynamics. Our results indicate that m\u03b22m low-aggregation propensity is due to two concomitant aspects: the low-aggregation propensity of its primary sequence combined with the absence of high-energy amyloid-competent conformations under native conditions. The identification of the specific properties determining the low-aggregation propensity of mouse \u03b22m will help delineate the molecular risk factors which cause a folded protein to aggregate.", "doi": "10.1111/febs.15046", "pmid": "31420997", "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:17:54.399Z", "modified": "2026-08-20T11:17:54.477Z"}]}