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PLoS One. 2016 Nov 28;11(11):e0167017. doi: 10.1371/journal.pone.0167017. eCollection 2016.

Characterization of the Canine MHC Class I DLA-88*50101 Peptide Binding Motif as a Prerequisite for Canine T Cell Immunotherapy.

Author information

1
Department of Immunology, Institute of Cell Biology, University of Tuebingen, Tuebingen, Germany.
2
Institute for Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
3
Immatics, Biotechnologies GmbH, Tuebingen, Germany.
4
Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
5
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
6
Applied Bioinformatics, Center of Bioinformatics and Department of Computer Science, University of Tuebingen, Tuebingen, Germany.

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.

PMID:
27893789
PMCID:
PMC5125661
DOI:
10.1371/journal.pone.0167017
[Indexed for MEDLINE]
Free PMC Article

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