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 journalArticle

Abstract

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
Volume6
Issue number10
DOIs
Publication statusPublished - Oct 2010

Fingerprint

Theileria parva
T-Cell Antigen Receptor
Epitopes
T-Lymphocytes
Peptides
Alleles
Social Dominance
Cattle Diseases
Parasitic Diseases
Adaptive Immunity
Parasites
Vaccines
Clone Cells

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.

Keywords

  • 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

Cite this

Macdonald, I. K., Harkiolaki, M., Hunt, L., Connelley, T., Carroll, A. V., MacHugh, N. D., ... Ellis, S. A. (2010). MHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors. Plos Pathogens, 6(10), e1001149. [e1001149]. https://doi.org/10.1371/journal.ppat.1001149
Macdonald, Isabel K. ; Harkiolaki, Maria ; Hunt, Lawrence ; Connelley, Timothy ; Carroll, A. Victoria ; MacHugh, Niall D. ; Graham, Simon P. ; Jones, E. Yvonne ; Morrison, W. Ivan ; Flower, Darren R ; Ellis, Shirley A. / MHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors. In: Plos Pathogens. 2010 ; Vol. 6, No. 10. pp. e1001149.
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Macdonald, IK, Harkiolaki, M, Hunt, L, Connelley, T, Carroll, AV, MacHugh, ND, Graham, SP, Jones, EY, Morrison, WI, Flower, DR & Ellis, SA 2010, 'MHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors', Plos Pathogens, vol. 6, no. 10, e1001149, pp. e1001149. https://doi.org/10.1371/journal.ppat.1001149

MHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors. / Macdonald, Isabel K.; Harkiolaki, Maria; Hunt, Lawrence; Connelley, Timothy; Carroll, A. Victoria; MacHugh, Niall D.; Graham, Simon P.; Jones, E. Yvonne; Morrison, W. Ivan; Flower, Darren R; Ellis, Shirley A.

In: Plos Pathogens, Vol. 6, No. 10, e1001149, 10.2010, p. e1001149.

Research output: Contribution to journalArticle

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T1 - MHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors

AU - Macdonald, Isabel K.

AU - Harkiolaki, Maria

AU - Hunt, Lawrence

AU - Connelley, Timothy

AU - Carroll, A. Victoria

AU - MacHugh, Niall D.

AU - Graham, Simon P.

AU - Jones, E. Yvonne

AU - Morrison, W. Ivan

AU - Flower, Darren R

AU - Ellis, Shirley A.

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