title: Characterization of the Canine MHC Class I DLA-88*50101 Peptide Binding Motif as a Prerequisite for Canine T Cell Immunotherapy.
abstract: There are limitations in pre-clinical settings using mice as a basis for clinical development in humans. In cancer, similarities exist between humans and dogs; thus, the dog patient can be a link in the transition from laboratory research on mouse models to clinical trials in humans. Knowledge of the peptides presented on MHC molecules is fundamental for the development of highly specific T cell-based immunotherapies. This information is available for human MHC molecules but is absent for the canine MHC. In the present study, we characterized the binding motif of dog leukocyte antigen (DLA) class I allele DLA-88*50101, using human C1R and K562 transfected cells expressing the DLA-88*50101 heavy chain. MHC class I immunoaffinity-purification revealed 3720 DLA-88*50101 derived peptides, which enabled the determination of major anchor positions. The characterized binding motif of DLA-88*50101 was similar to HLA-A*02:01. Peptide binding analyses on HLA-A*02:01 and DLA-88*50101 via flow cytometry showed weak binding of DLA-88*50101 derived peptides to HLA-A*02:01, and vice versa. Our results present for the first time a detailed peptide binding motif of the canine MHC class I allelic product DLA-88*50101. These data support the goal of establishing dogs as a suitable animal model for the evaluation and development of T cell-based cancer immunotherapies, benefiting both dog and human patients.
authors.affiliation: Department of Immunology, Institute of Cell Biology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Barth
authors.affiliation: Department of Immunology, Institute of Cell Biology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Schreitmüller
authors.affiliation: Department of Immunology, Institute of Cell Biology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Proehl
authors.affiliation: Department of Immunology, Institute of Cell Biology, University of Tuebingen, Tuebingen, Germany.|Institute for Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Oehl
authors.affiliation: Department of Immunology, Institute of Cell Biology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Leonie M
authors.initials: LM
authors.lastname: Lumpp
authors.affiliation: Department of Immunology, Institute of Cell Biology, University of Tuebingen, Tuebingen, Germany.|Immatics, Biotechnologies GmbH, Tuebingen, Germany.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kowalewski
authors.affiliation: Department of Immunology, Institute of Cell Biology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Moreno
authors.initials: M
authors.lastname: Di Marco
authors.affiliation: Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.|Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Theo
authors.initials: T
authors.lastname: Sturm
authors.affiliation: Department of Immunology, Institute of Cell Biology, University of Tuebingen, Tuebingen, Germany.|Applied Bioinformatics, Center of Bioinformatics and Department of Computer Science, University of Tuebingen, Tuebingen, Germany.
authors.forename: Linus
authors.initials: L
authors.lastname: Backert
authors.affiliation: Department of Immunology, Institute of Cell Biology, University of Tuebingen, Tuebingen, Germany.|Institute for Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Heiko
authors.initials: H
authors.lastname: Schuster
authors.affiliation: Department of Immunology, Institute of Cell Biology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanović
authors.affiliation: Department of Immunology, Institute of Cell Biology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.affiliation: Department of Immunology, Institute of Cell Biology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Planz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004283:Dog Diseases / Q000276:immunology* / Q000628:therapy*; D004285:Dogs; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D020014:K562 Cells; D051379:Mice; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments