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dc.contributor.authorBilal, Sumaira
dc.contributor.authorLie, Kai Kristoffer
dc.contributor.authorSæle, Øystein
dc.contributor.authorHordvik, Ivar
dc.PublishedBilal S, Lie Kk, Sæle Ø, Hordvik I. T cell receptor alpha chain genes in the teleost Ballan wrasse (Labrus bergylta) are subjected to somatic hypermutation. Frontiers in Immunology. 2018;9:1101eng
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).en_US
dc.publisherFrontiers Mediaen_US
dc.rightsAttribution CC BYeng
dc.subjectT cell receptoreng
dc.subjectballan wrasseeng
dc.subjectsomatic hypermutationeng
dc.subjectactivation-induced cytidine deaminase motifeng
dc.titleT cell receptor alpha chain genes in the teleost Ballan wrasse (Labrus bergylta) are subjected to somatic hypermutationen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2018 The Authorsen_US
dc.source.journalFrontiers in Immunology
dc.relation.projectNorges forskningsråd: 244396

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