MHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors

Isabel K. Macdonald, Maria Harkiolaki, Lawrence Hunt, Timothy Connelley, A. Victoria Carroll, Niall D. MacHugh, Simon P. Graham, E. Yvonne Jones, W. Ivan Morrison, Darren R Flower, Shirley A. Ellis

Research output: Contribution to journalArticlepeer-review


T cell receptor (TCR) recognition of peptide-MHC class I (pMHC) complexes is a crucial event in the adaptive immune response to pathogens. Peptide epitopes often display a strong dominance hierarchy, resulting in focusing of the response on a limited number of the most dominant epitopes. Such T cell responses may be additionally restricted by particular MHC alleles in preference to others. We have studied this poorly understood phenomenon using Theileria parva, a protozoan parasite that causes an often fatal lymphoproliferative disease in cattle. Despite its antigenic complexity, CD8+ T cell responses induced by infection with the parasite show profound immunodominance, as exemplified by the Tp1(214-224) epitope presented by the common and functionally important MHC class I allele N*01301. We present a high-resolution crystal structure of this pMHC complex, demonstrating that the peptide is presented in a distinctive raised conformation. Functional studies using CD8+ T cell clones show that this impacts significantly on TCR recognition. The unconventional structure is generated by a hydrophobic ridge within the MHC peptide binding groove, found in a set of cattle MHC alleles. Extremely rare in all other species, this feature is seen in a small group of mouse MHC class I molecules. The data generated in this analysis contribute to our understanding of the structural basis for T cell-dependent immune responses, providing insight into what determines a highly immunogenic p-MHC complex, and hence can be of value in prediction of antigenic epitopes and vaccine design.
Original languageEnglish
Article numbere1001149
Pages (from-to)e1001149
JournalPlos Pathogens
Issue number10
Publication statusPublished - Oct 2010

Bibliographical note

© 2010 Macdonald et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


  • amino acid sequence
  • animals
  • antigen presentation
  • binding sites
  • CD8-positive T-lymphocytes
  • cattle
  • crystallography
  • histocompatibility antigens class I
  • immunodominant epitopes
  • mice
  • molecular models
  • protein binding
  • protein conformation
  • antigen receptors
  • theileria parva
  • T-cell


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