High-resolution description of antibody heavy-chain repertoires in humans.

Antibodies' protective, pathological, and therapeutic properties result from their considerable diversity. This diversity is almost limitless in potential, but actual diversity is still poorly understood. Here we use deep sequencing to characterize the diversity of the heavy-chain CDR3 region,...

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Main Authors: Ramy Arnaout, William Lee, Patrick Cahill, Tracey Honan, Todd Sparrow, Michael Weiand, Chad Nusbaum, Klaus Rajewsky, Sergei B Koralov
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3150326?pdf=render
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author Ramy Arnaout
William Lee
Patrick Cahill
Tracey Honan
Todd Sparrow
Michael Weiand
Chad Nusbaum
Klaus Rajewsky
Sergei B Koralov
author_facet Ramy Arnaout
William Lee
Patrick Cahill
Tracey Honan
Todd Sparrow
Michael Weiand
Chad Nusbaum
Klaus Rajewsky
Sergei B Koralov
author_sort Ramy Arnaout
collection DOAJ
description Antibodies' protective, pathological, and therapeutic properties result from their considerable diversity. This diversity is almost limitless in potential, but actual diversity is still poorly understood. Here we use deep sequencing to characterize the diversity of the heavy-chain CDR3 region, the most important contributor to antibody binding specificity, and the constituent V, D, and J segments that comprise it. We find that, during the stepwise D-J and then V-DJ recombination events, the choice of D and J segments exert some bias on each other; however, we find the choice of the V segment is essentially independent of both. V, D, and J segments are utilized with different frequencies, resulting in a highly skewed representation of VDJ combinations in the repertoire. Nevertheless, the pattern of segment usage was almost identical between two different individuals. The pattern of V, D, and J segment usage and recombination was insufficient to explain overlap that was observed between the two individuals' CDR3 repertoires. Finally, we find that while there are a near-infinite number of heavy-chain CDR3s in principle, there are about 3-9 million in the blood of an adult human being.
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spelling doaj.art-366191ef8b674e9092ec9288e83a5c4b2022-12-21T19:17:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0168e2236510.1371/journal.pone.0022365High-resolution description of antibody heavy-chain repertoires in humans.Ramy ArnaoutWilliam LeePatrick CahillTracey HonanTodd SparrowMichael WeiandChad NusbaumKlaus RajewskySergei B KoralovAntibodies' protective, pathological, and therapeutic properties result from their considerable diversity. This diversity is almost limitless in potential, but actual diversity is still poorly understood. Here we use deep sequencing to characterize the diversity of the heavy-chain CDR3 region, the most important contributor to antibody binding specificity, and the constituent V, D, and J segments that comprise it. We find that, during the stepwise D-J and then V-DJ recombination events, the choice of D and J segments exert some bias on each other; however, we find the choice of the V segment is essentially independent of both. V, D, and J segments are utilized with different frequencies, resulting in a highly skewed representation of VDJ combinations in the repertoire. Nevertheless, the pattern of segment usage was almost identical between two different individuals. The pattern of V, D, and J segment usage and recombination was insufficient to explain overlap that was observed between the two individuals' CDR3 repertoires. Finally, we find that while there are a near-infinite number of heavy-chain CDR3s in principle, there are about 3-9 million in the blood of an adult human being.http://europepmc.org/articles/PMC3150326?pdf=render
spellingShingle Ramy Arnaout
William Lee
Patrick Cahill
Tracey Honan
Todd Sparrow
Michael Weiand
Chad Nusbaum
Klaus Rajewsky
Sergei B Koralov
High-resolution description of antibody heavy-chain repertoires in humans.
PLoS ONE
title High-resolution description of antibody heavy-chain repertoires in humans.
title_full High-resolution description of antibody heavy-chain repertoires in humans.
title_fullStr High-resolution description of antibody heavy-chain repertoires in humans.
title_full_unstemmed High-resolution description of antibody heavy-chain repertoires in humans.
title_short High-resolution description of antibody heavy-chain repertoires in humans.
title_sort high resolution description of antibody heavy chain repertoires in humans
url http://europepmc.org/articles/PMC3150326?pdf=render
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