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

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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/dc0bc3cc205e45e6bb0790896cba9fc0
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spelling	oai:doaj.org-article:dc0bc3cc205e45e6bb0790896cba9fc02021-11-18T06:03:49ZMHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors.1553-73661553-737410.1371/journal.ppat.1001149https://doaj.org/article/dc0bc3cc205e45e6bb0790896cba9fc02010-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20976198/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374T 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.Isabel K MacdonaldMaria HarkiolakiLawrence HuntTimothy ConnelleyA Victoria CarrollNiall D MacHughSimon P GrahamE Yvonne JonesW Ivan MorrisonDarren R FlowerShirley A EllisPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 10, p e1001149 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 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 MHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors.
description	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.
format	article
author	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
author_facet	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
author_sort	Isabel K Macdonald
title	MHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors.
title_short	MHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors.
title_full	MHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors.
title_fullStr	MHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors.
title_full_unstemmed	MHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors.
title_sort	mhc class i bound to an immunodominant theileria parva epitope demonstrates unconventional presentation to t cell receptors.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/dc0bc3cc205e45e6bb0790896cba9fc0
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MHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors.

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