Functional characterization of human terminal deoxynucleotidyl transferase polymorphisms

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dc.contributor.advisorWu, Gillian E.
dc.contributor.advisorSheng, Yi
dc.creatorTroshchynsky, Anna
dc.date.accessioned2016-09-13T13:15:32Z
dc.date.available2016-09-13T13:15:32Z
dc.date.copyright2013-09
dc.degree.disciplineBiology
dc.degree.levelMaster's
dc.degree.nameMSc - Master of Science
dc.description.abstractTerminal deoxynucleotidyl transferase (TdT) contributes to antigen receptor diversity of B and T lymphocytes of the adaptive immune system. TdT is a DNA polymerase catalyzing template independent addition of nucleotides during the process of V(D)J recombination. This thesis investigates whether the polymerase activities of naturally occurring single nucleotide polymorphic (SNP) forms of human TdT vary and the possible effects on the antigen receptor repertoire. Two SNPs (A445T/L397S) demonstrated significantly lower in vitro polymerization activities compared to the wild type enzyme, while one (R431C) was completely inactive. In vivo extrachromosomal recombination assay demonstrated over 3 fold difference in the proportion of N-containing joints and significantly lower numbers of N-nucleotides per joint for both L397S and R431C variants compared to WT hTdTS. Variability in enzymatic activities of the SNPs may affect the diversity of antigen receptors, thus potentially impact the downstream adaptive immune response in healthy and autoimmune-prone individuals possessing these SNPs.
dc.identifier.urihttp://hdl.handle.net/10315/32021
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subject.keywordsdeoxynucleotidyl transferase polymorphisms
dc.subject.keywordsterminal deoxynucleotidyl transferase
dc.subject.keywordsTdT
dc.subject.keywordsL397S
dc.subject.keywordsR431C
dc.titleFunctional characterization of human terminal deoxynucleotidyl transferase polymorphisms
dc.typeElectronic Thesis or Dissertation

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