title: Toxoplasma gondii peptide ligands open the gate of the HLA class I binding groove.
abstract: HLA class I presentation of pathogen-derived peptide ligands is essential for CD8+ T-cell recognition of Toxoplasma gondii infected cells. Currently, little data exist pertaining to peptides that are presented after T. gondii infection. Herein we purify HLA-A*02:01 complexes from T. gondii infected cells and characterize the peptide ligands using LCMS. We identify 195 T. gondii encoded ligands originating from both secreted and cytoplasmic proteins. Surprisingly, T. gondii ligands are significantly longer than uninfected host ligands, and these longer pathogen-derived peptides maintain a canonical N-terminal binding core yet exhibit a C-terminal extension of 1-30 amino acids. Structural analysis demonstrates that binding of extended peptides opens the HLA class I F' pocket, allowing the C-terminal extension to protrude through one end of the binding groove. In summary, we demonstrate that unrealized structural flexibility makes MHC class I receptive to parasite-derived ligands that exhibit unique C-terminal peptide extensions.
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, United States.|Pure MHC LLC, Austin, United States.
authors.forename: Curtis
authors.identifier: http://orcid.org/0000-0003-4540-4140
authors.initials: C
authors.lastname: McMurtrey
authors.affiliation: Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark.|La Jolla Institute for Allergy and Immunology, La Jolla, United States.
authors.forename: Thomas
authors.identifier: http://orcid.org/0000-0003-0762-2198
authors.initials: T
authors.lastname: Trolle
authors.affiliation: Department of Microbiology and Immunology, University at Buffalo School of Medicine, Buffalo, United States.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Sansom
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, United States.
authors.forename: Soumya G
authors.initials: SG
authors.lastname: Remesh
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, United States.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kaever
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, United States.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Bardet
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, United States.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Jackson
authors.affiliation: University of Chicago, Chicago, United States.
authors.forename: Rima
authors.initials: R
authors.lastname: McLeod
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, United States.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.affiliation: Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark.|Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, Buenos Aires, Argentina.
authors.forename: Morten
authors.initials: M
authors.lastname: Nielsen
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, United States.
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Zajonc
authors.affiliation: Department of Microbiology and Immunology, University at Buffalo School of Medicine, Buffalo, United States.
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Blader
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, United States.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Peters
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, United States.|Pure MHC LLC, Austin, United States.
authors.forename: William
authors.initials: W
authors.lastname: Hildebrand
mesh_terms: D000953:Antigens, Protozoan / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D009000:Monocytes / Q000276:immunology* / Q000469:parasitology; D011485:Protein Binding; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism*; D014122:Toxoplasma / Q000737:chemistry* / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D015395:Histocompatibility Antigens Class I; D015800:Protozoan Proteins
keywords: HLA; T. gondii; crystallography; human; immunology; infectious disease; mass spectrometry; microbiology; peptide ligands
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