Functional analyses of polymorphic variants of human terminal deoxynucleotidyl transferase.
A Troshchynsky, I Dzneladze, L Chen, Y Sheng, V Saridakis, G E Wu
文献索引:Genes Immun. 16 , 388-98, (2015)
全文:HTML全文
摘要
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.
相关化合物
相关文献:
2014-08-01
[Mol. Plant 7(8) , 1365-83, (2014)]
2014-12-11
[Oncogene 33(50) , 5688-96, (2014)]
2015-02-20
[Oncotarget 6(5) , 2604-14, (2015)]
2015-04-13
[Biomacromolecules 16(4) , 1382-9, (2015)]
2015-04-01
[J. Pineal Res. 58(3) , 310-20, (2015)]