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Functional analyses of polymorphic variants of human terminal deoxynucleotidyl transferase.

Human terminal deoxynucleotidyl transferase (hTdT) is a DNA polymerase that functions to generate diversity in the adaptive immune system. Here, we focus on the function of naturally occurring single-nucleotide polymorphisms (SNPs) of hTdT to evaluate their role in genetic-generated immune variation... Full description

Journal Title: Genes and immunity September 2015, Vol.16(6), pp.388-398
Main Author: Troshchynsky, A
Other Authors: Dzneladze, I , Chen, L , Sheng, Y , Saridakis, V , Wu, G E
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1476-5470 ; DOI: 10.1038/gene.2015.19
Link: http://search.proquest.com/docview/1709705661/?pq-origsite=primo
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recordid: proquest1709705661
title: Functional analyses of polymorphic variants of human terminal deoxynucleotidyl transferase.
format: Article
creator:
  • Troshchynsky, A
  • Dzneladze, I
  • Chen, L
  • Sheng, Y
  • Saridakis, V
  • Wu, G E
subjects:
  • Adaptive Immunity–Genetics
  • DNA Nucleotidylexotransferase–Chemistry
  • Humans–Genetics
  • Immunoglobulin Variable Region–Metabolism
  • Jurkat Cells–Genetics
  • Models, Molecular–Genetics
  • Nucleotides–Genetics
  • Polymorphism, Single Nucleotide–Genetics
  • Receptors, Antigen, T-Cell–Genetics
  • V(D)J Recombination–Genetics
  • Immunoglobulin Variable Region
  • Nucleotides
  • Receptors, Antigen, T-Cell
  • DNA Nucleotidylexotransferase
ispartof: Genes and immunity, September 2015, Vol.16(6), pp.388-398
description: Human terminal deoxynucleotidyl transferase (hTdT) is a DNA polymerase that functions to generate diversity in the adaptive immune system. Here, we focus on the function of naturally occurring single-nucleotide polymorphisms (SNPs) of hTdT to evaluate their role in genetic-generated immune variation. The data demonstrate that the genetic variations generated by the hTdT SNPs will vary the human immune repertoire and thus its responses. Human TdT catalyzes template- independent addition of nucleotides (N-additions) during coding joint formation in V(D)J recombination. Its activity is crucial to the diversity of the antigen receptors of B and T lymphocytes. We used in vitro polymerase assays and in vivo human cell V(D)J recombination assays to evaluate the activity and the N-addition levels of six natural (SNP) variants of hTdT. In vitro, the variants differed from wild-type hTdT in polymerization ability with four having significantly lower activity. In vivo, the presence of TdT varied both the efficiency of recombination and N-addition, with two variants generating coding joints with significantly fewer N-additions. Although likely heterozygous, individuals possessing these genetic changes may have less diverse B- and T-cell receptors that would particularly effect individuals prone to adaptive immune disorders, including autoimmunity. Genes and Immunity (2015) 16, 388-398;doi: 10.1038/gene.2015.19;published online 4 June 2015
language: eng
source:
identifier: E-ISSN: 1476-5470 ; DOI: 10.1038/gene.2015.19
fulltext: fulltext
issn:
  • 14765470
  • 1476-5470
url: Link


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titleFunctional analyses of polymorphic variants of human terminal deoxynucleotidyl transferase.
creatorTroshchynsky, A ; Dzneladze, I ; Chen, L ; Sheng, Y ; Saridakis, V ; Wu, G E
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ispartofGenes and immunity, September 2015, Vol.16(6), pp.388-398
identifierE-ISSN: 1476-5470 ; DOI: 10.1038/gene.2015.19
subjectAdaptive Immunity–Genetics ; DNA Nucleotidylexotransferase–Chemistry ; Humans–Genetics ; Immunoglobulin Variable Region–Metabolism ; Jurkat Cells–Genetics ; Models, Molecular–Genetics ; Nucleotides–Genetics ; Polymorphism, Single Nucleotide–Genetics ; Receptors, Antigen, T-Cell–Genetics ; V(D)J Recombination–Genetics ; Immunoglobulin Variable Region ; Nucleotides ; Receptors, Antigen, T-Cell ; DNA Nucleotidylexotransferase
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descriptionHuman terminal deoxynucleotidyl transferase (hTdT) is a DNA polymerase that functions to generate diversity in the adaptive immune system. Here, we focus on the function of naturally occurring single-nucleotide polymorphisms (SNPs) of hTdT to evaluate their role in genetic-generated immune variation. The data demonstrate that the genetic variations generated by the hTdT SNPs will vary the human immune repertoire and thus its responses. Human TdT catalyzes template- independent addition of nucleotides (N-additions) during coding joint formation in V(D)J recombination. Its activity is crucial to the diversity of the antigen receptors of B and T lymphocytes. We used in vitro polymerase assays and in vivo human cell V(D)J recombination assays to evaluate the activity and the N-addition levels of six natural (SNP) variants of hTdT. In vitro, the variants differed from wild-type hTdT in polymerization ability with four having significantly lower activity. In vivo, the presence of TdT varied both the efficiency of recombination and N-addition, with two variants generating coding joints with significantly fewer N-additions. Although likely heterozygous, individuals possessing these genetic changes may have less diverse B- and T-cell receptors that would particularly effect individuals prone to adaptive immune disorders, including autoimmunity. Genes and Immunity (2015) 16, 388-398;doi: 10.1038/gene.2015.19;published online 4 June 2015
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