MHC Class I Bound to an Immunodominant Theileria parva Epitope Demonstrates Unconventional Presentation to T Cell Receptors

Macdonald, IK, Harkiolaki, M, Hunt, L, Connelley, T, Carroll, AV, MacHugh, ND, Graham, SP, Jones, EY, Morrison, WI, Flower, DR et al and Ellis, SA (2010) MHC Class I Bound to an Immunodominant Theileria parva Epitope Demonstrates Unconventional Presentation to T Cell Receptors PLOS PATHOGENS, 6 (10), ARTN e1001.

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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 Tp1214–224 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.

Item Type:	Article
Subjects :	Veterinary Medicine
Divisions :	Faculty of Health and Medical Sciences > School of Veterinary Medicine
Authors :	Name Email ORCID Macdonald, IK Harkiolaki, M Hunt, L Connelley, T Carroll, AV MacHugh, ND Graham, SP Jones, EY Morrison, WI Flower, DR Ellis, SA
Date :	1 October 2010
DOI :	10.1371/journal.ppat.1001149
Copyright Disclaimer :	Copyright 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.
Uncontrolled Keywords :	Science & Technology, Life Sciences & Biomedicine, Microbiology, Parasitology, Virology, MICROBIOLOGY, PARASITOLOGY, VIROLOGY, MAJOR HISTOCOMPATIBILITY COMPLEX, PEPTIDE, CATTLE, GENES, RESPONSES, BINDING, MOLECULES, ANTIGENS, RESOLUTION, HAPLOTYPES
Related URLs :	Author
Additional Information :	Copyright 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.
Depositing User :	Symplectic Elements
Date Deposited :	22 Mar 2016 15:37
Last Modified :	31 Oct 2017 18:07
URI:	http://epubs.surrey.ac.uk/id/eprint/810177

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