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

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

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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Dog Diseases / immunology*
  • Dog Diseases / therapy*
  • Dogs
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunotherapy*
  • K562 Cells
  • Mice
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology*
  • Peptide Fragments / metabolism
  • Polymorphism, Genetic / genetics
  • Protein Binding
  • Sequence Homology, Amino Acid
  • T-Lymphocytes / immunology*

Substances

  • Histocompatibility Antigens Class I
  • Peptide Fragments

Grant support

The funders Immatics, Biotechnologies GmbH, Biomolecular Mass Spectrometry and Proteomics provided no support in the form of salaries for authors [D.K., H.S. and T.S], and did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.