Peptide-binding motifs of two common equine class I MHC molecules in Thoroughbred horses

Abstract

Quantitative peptide-binding motifs of MHC class I alleles provide a valuable tool to efficiently identify putative T cell epitopes. Detailed information on equine MHC class I alleles is still very limited, and to date, only a single equine MHC class I allele, Eqca-1*00101 (ELA-A3 haplotype), has been characterized. The present study extends the number of characterized ELA class I specificities in two additional haplotypes found commonly in the Thoroughbred breed. Accordingly, we here report quantitative binding motifs for the ELA-A2 allele Eqca-16*00101 and the ELA-A9 allele Eqca-1*00201. Utilizing analyses of endogenously bound and eluted ligands and the screening of positional scanning combinatorial libraries, detailed and quantitative peptide-binding motifs were derived for both alleles. Eqca-16*00101 preferentially binds peptides with aliphatic/hydrophobic residues in position 2 and at the C-terminus, and Eqca-1*00201 has a preference for peptides with arginine in position 2 and hydrophobic/aliphatic residues at the C-terminus. Interestingly, the Eqca-16*00101 motif resembles that of the human HLA A02-supertype, while the Eqca-1*00201 motif resembles that of the HLA B27-supertype and two macaque class I alleles. It is expected that the identified motifs will facilitate the selection of candidate epitopes for the study of immune responses in horses.

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Acknowledgements

The present work has been supported by funds provided through NIH NIAID contracts HHSN272200900042C and HHSN272201400045C, NIH U19AI090023 (Sette), NIH R01AI112566 (Sidney) and NIH AI 033993 (Hunt), the Harry M. Zweig Memorial Fund for Equine Research (Antczak), and Morris Animal Foundation grant D12EQ-026 (Antczak). DFA is an Investigator of the Dorothy Russell Havemeyer Foundation, Inc.

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Correspondence to Alessandro Sette.

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Bergmann, T., Lindvall, M., Moore, E. et al. Peptide-binding motifs of two common equine class I MHC molecules in Thoroughbred horses. Immunogenetics 69, 351–358 (2017). https://doi.org/10.1007/s00251-017-0978-6

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Keywords

  • MHC class I
  • Peptide binding
  • MHC binding motif
  • T cell epitope
  • Equus caballus (Eqca)