{"entity": "researcher", "timestamp": "2026-10-07T13:39:35.639Z", "family": "Buratto", "given": "Jeremie", "initials": "J", "orcid": "0000-0002-6730-336X", "affiliations": ["Science for Life Laboratory, Department of Medicine, Solna, Karolinska Institutet, SE-10450 Stockholm, Sweden; and."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/e545d60bef4b48f8aef968e5e566252c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/e545d60bef4b48f8aef968e5e566252c"}}, "publications": [{"entity": "publication", "iuid": "5df61ebdafd04b79a269e0d2b0cc36fb", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5df61ebdafd04b79a269e0d2b0cc36fb.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5df61ebdafd04b79a269e0d2b0cc36fb"}}, "title": "The MHC Class I Cancer-Associated Neoepitope Trh4 Linked with Impaired Peptide Processing Induces a Unique Noncanonical TCR Conformer.", "authors": [{"family": "Hafstrand", "given": "Ida", "initials": "I"}, {"family": "Doorduijn", "given": "Elien M", "initials": "EM"}, {"family": "Duru", "given": "Adil Doganay", "initials": "AD"}, {"family": "Buratto", "given": "Jeremie", "initials": "J", "orcid": "0000-0002-6730-336X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e545d60bef4b48f8aef968e5e566252c.json"}}, {"family": "Oliveira", "given": "Claudia Cunha", "initials": "CC"}, {"family": "Sandalova", "given": "Tatyana", "initials": "T"}, {"family": "van Hall", "given": "Thorbald", "initials": "T"}, {"family": "Achour", "given": "Adnane", "initials": "A", "orcid": "0000-0003-0432-710X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/65fba324156a4fcbafbe636e642587a9.json"}}], "type": "journal article", "published": "2016-03-01", "journal": {"title": "J. Immunol.", "issn": "1550-6606", "volume": "196", "issue": "5", "pages": "2327-2334", "issn-l": "0022-1767"}, "abstract": "MHC class I downregulation represents a significant challenge for successful T cell-based immunotherapy. T cell epitopes associated with impaired peptide processing (TEIPP) constitute a novel category of immunogenic Ags that are selectively presented on transporter associated with Ag processing-deficient cells. The TEIPP neoepitopes are CD8 T cell targets, derived from nonmutated self-proteins that might be exploited to prevent immune escape. In this study, the crystal structure of H-2D(b) in complex with the first identified TEIPP Ag (MCLRMTAVM) derived from the Trh4 protein has been determined to 2.25 \u00c5 resolution. In contrast to prototypic H-2D(b) peptides, Trh4 takes a noncanonical peptide-binding pattern with extensive sulfur-\u03c0 interactions that contribute to the overall complex stability. Importantly, the noncanonical methionine at peptide position 5 acts as a main anchor, altering only the conformation of the H-2D(b) residues Y156 and H155 and thereby forming a unique MHC/peptide conformer that is essential for recognition by TEIPP-specific T cells. Substitution of peptide residues p2C and p5M to the conservative \u03b1-aminobutyric acid and norleucine, respectively, significantly reduced complex stability, without altering peptide conformation or T cell recognition. In contrast, substitution of p5M to a conventional asparagine abolished recognition by the H-2D(b)/Trh4-specific T cell clone LnB5. We anticipate that the H-2D(b)/Trh4 complex represents the first example, to our knowledge, of a broader repertoire of alternative MHC class I binders.", "doi": "10.4049/jimmunol.1502249", "pmid": "26800871", "labels": [], "xrefs": [{"db": "pii", "key": "jimmunol.1502249"}], "notes": [], "created": "2018-12-05T12:18:11.109Z", "modified": "2026-09-23T12:01:41.747Z"}]}