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dc.contributor.authorBilal, Sumaira
dc.contributor.authorLie, Kai Kristoffer
dc.contributor.authorSæle, Øystein
dc.contributor.authorHordvik, Ivar
dc.date.accessioned2018-09-05T12:30:03Z
dc.date.available2018-09-05T12:30:03Z
dc.date.created2018-06-21T19:53:31Z
dc.date.issued2018
dc.identifier.citationFrontiers in Immunology. 2018, 9:1101 (MAY), 1-11.nb_NO
dc.identifier.issn1664-3224
dc.identifier.urihttp://hdl.handle.net/11250/2560994
dc.description.abstractPreviously, somatic hypermutation (SHM) was considered to be exclusively associated with affinity maturation of antibodies, although it also occurred in T cells under certain conditions. More recently, it has been shown that SHM generates diversity in the variable domain of T cell receptor (TCR) in camel and shark. Here, we report somatic mutations in TCR alpha chain genes of the teleost fish, Ballan wrasse (Labrus bergylta), and show that this mechanism adds extra diversity to the polymorphic constant (C) region as well. The organization of the TCR alpha/delta locus in Ballan wrasse was obtained from a scaffold covering a single copy C alpha gene, 65 putative J alpha segments, a single copy C delta gene, 1 J delta segment, and 2 D delta segments. Analysis of 37 fish revealed 6 allotypes of the C alpha gene, each with 1–3 replacement substitutions. Somatic mutations were analyzed by molecular cloning of TCR alpha chain cDNA. Initially, 79 unique clones comprising four families of variable (V) alpha genes were characterized. Subsequently, a more restricted PCR was performed to focus on a specific V gene. Comparison of 48 clones indicated that the frequency of somatic mutations in the VJ region was 4.5/1,000 base pairs (bps), and most prevalent in complementary determining region 2 (CDR2). In total, 45 different J segments were identified among the 127 cDNA clones, counting for most of the CDR3 diversity. The number of mutations in the C alpha chain gene was 1.76 mutations/1,000 bps and A nucleotides were most frequently targeted, in contrast to the VJ region, where G nucleotides appeared to be mutational hotspots. The replacement/synonymous ratios in the VJ and C regions were 2.5 and 1.85, respectively. Only 7% of the mutations were found to be linked to the activation-induced cytidine deaminase hotspot motif (RGYW/WRCY).nb_NO
dc.language.isoengnb_NO
dc.titleT cell receptor alpha chain genes in the teleost Ballan wrasse (Labrus bergylta) are subjected to somatic hypermutationnb_NO
dc.title.alternativeT cell receptor alpha chain genes in the teleost Ballan wrasse (Labrus bergylta) are subjected to somatic hypermutationnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.description.versionpublishedVersionnb_NO
dc.source.pagenumber1-11nb_NO
dc.source.volume9:1101nb_NO
dc.source.journalFrontiers in Immunologynb_NO
dc.source.issueMAYnb_NO
dc.identifier.doi10.3389/fimmu.2018.01101
dc.identifier.cristin1593032
dc.relation.projectNorges forskningsråd: 244396nb_NO
cristin.unitcode7431,32,0,0
cristin.unitcode7431,31,0,0
cristin.unitnameTrygt fôr
cristin.unitnameBehov og velferd
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1


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