Genetic and structural basis for selection of a ubiquitous T cell receptor deployed in Epstein-Barr virus infection.

Despite the ∼10(18) αβ T cell receptor (TCR) structures that can be randomly manufactured by the human thymus, some surface more frequently than others. The pinnacles of this distortion are public TCRs, which exhibit amino acid-identical structures across different individuals. Public TCRs are thoug...

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Autores principales:	John J Miles, Anna M Bulek, David K Cole, Emma Gostick, Andrea J A Schauenburg, Garry Dolton, Vanessa Venturi, Miles P Davenport, Mai Ping Tan, Scott R Burrows, Linda Wooldridge, David A Price, Pierre J Rizkallah, Andrew K Sewell
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/306c4ef650b24c9d8ee4fe6f2fc17f93
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spelling	oai:doaj.org-article:306c4ef650b24c9d8ee4fe6f2fc17f932021-11-18T06:05:17ZGenetic and structural basis for selection of a ubiquitous T cell receptor deployed in Epstein-Barr virus infection.1553-73661553-737410.1371/journal.ppat.1001198https://doaj.org/article/306c4ef650b24c9d8ee4fe6f2fc17f932010-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21124993/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Despite the ∼10(18) αβ T cell receptor (TCR) structures that can be randomly manufactured by the human thymus, some surface more frequently than others. The pinnacles of this distortion are public TCRs, which exhibit amino acid-identical structures across different individuals. Public TCRs are thought to result from both recombinatorial bias and antigen-driven selection, but the mechanisms that underlie inter-individual TCR sharing are still largely theoretical. To examine this phenomenon at the atomic level, we solved the co-complex structure of one of the most widespread and numerically frequent public TCRs in the human population. The archetypal AS01 public TCR recognizes an immunodominant BMLF1 peptide, derived from the ubiquitous Epstein-Barr virus, bound to HLA-A0201. The AS01 TCR was observed to dock in a diagonal fashion, grasping the solvent exposed peptide crest with two sets of complementarity-determining region (CDR) loops, and was fastened to the peptide and HLA-A0201 platform with residue sets found only within TCR genes biased in the public response. Computer simulations of a random V(D)J recombination process demonstrated that both TCRα and TCRβ amino acid sequences could be manufactured easily, thereby explaining the prevalence of this receptor across different individuals. Interestingly, the AS01 TCR was encoded largely by germline DNA, indicating that the TCR loci already comprise gene segments that specifically recognize this ancient pathogen. Such pattern recognition receptor-like traits within the αβ TCR system further blur the boundaries between the adaptive and innate immune systems.John J MilesAnna M BulekDavid K ColeEmma GostickAndrea J A SchauenburgGarry DoltonVanessa VenturiMiles P DavenportMai Ping TanScott R BurrowsLinda WooldridgeDavid A PricePierre J RizkallahAndrew K SewellPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 11, p e1001198 (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 John J Miles Anna M Bulek David K Cole Emma Gostick Andrea J A Schauenburg Garry Dolton Vanessa Venturi Miles P Davenport Mai Ping Tan Scott R Burrows Linda Wooldridge David A Price Pierre J Rizkallah Andrew K Sewell Genetic and structural basis for selection of a ubiquitous T cell receptor deployed in Epstein-Barr virus infection.
description	Despite the ∼10(18) αβ T cell receptor (TCR) structures that can be randomly manufactured by the human thymus, some surface more frequently than others. The pinnacles of this distortion are public TCRs, which exhibit amino acid-identical structures across different individuals. Public TCRs are thought to result from both recombinatorial bias and antigen-driven selection, but the mechanisms that underlie inter-individual TCR sharing are still largely theoretical. To examine this phenomenon at the atomic level, we solved the co-complex structure of one of the most widespread and numerically frequent public TCRs in the human population. The archetypal AS01 public TCR recognizes an immunodominant BMLF1 peptide, derived from the ubiquitous Epstein-Barr virus, bound to HLA-A0201. The AS01 TCR was observed to dock in a diagonal fashion, grasping the solvent exposed peptide crest with two sets of complementarity-determining region (CDR) loops, and was fastened to the peptide and HLA-A0201 platform with residue sets found only within TCR genes biased in the public response. Computer simulations of a random V(D)J recombination process demonstrated that both TCRα and TCRβ amino acid sequences could be manufactured easily, thereby explaining the prevalence of this receptor across different individuals. Interestingly, the AS01 TCR was encoded largely by germline DNA, indicating that the TCR loci already comprise gene segments that specifically recognize this ancient pathogen. Such pattern recognition receptor-like traits within the αβ TCR system further blur the boundaries between the adaptive and innate immune systems.
format	article
author	John J Miles Anna M Bulek David K Cole Emma Gostick Andrea J A Schauenburg Garry Dolton Vanessa Venturi Miles P Davenport Mai Ping Tan Scott R Burrows Linda Wooldridge David A Price Pierre J Rizkallah Andrew K Sewell
author_facet	John J Miles Anna M Bulek David K Cole Emma Gostick Andrea J A Schauenburg Garry Dolton Vanessa Venturi Miles P Davenport Mai Ping Tan Scott R Burrows Linda Wooldridge David A Price Pierre J Rizkallah Andrew K Sewell
author_sort	John J Miles
title	Genetic and structural basis for selection of a ubiquitous T cell receptor deployed in Epstein-Barr virus infection.
title_short	Genetic and structural basis for selection of a ubiquitous T cell receptor deployed in Epstein-Barr virus infection.
title_full	Genetic and structural basis for selection of a ubiquitous T cell receptor deployed in Epstein-Barr virus infection.
title_fullStr	Genetic and structural basis for selection of a ubiquitous T cell receptor deployed in Epstein-Barr virus infection.
title_full_unstemmed	Genetic and structural basis for selection of a ubiquitous T cell receptor deployed in Epstein-Barr virus infection.
title_sort	genetic and structural basis for selection of a ubiquitous t cell receptor deployed in epstein-barr virus infection.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/306c4ef650b24c9d8ee4fe6f2fc17f93
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Genetic and structural basis for selection of a ubiquitous T cell receptor deployed in Epstein-Barr virus infection.

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