In addition to canonical TCR and BCR, cartilaginous fish assemble noncanonical TCR that employ various B‐cell components. For example, shark T cells associate alpha (TCR‐α) or delta (TCR‐δ) constant (C) regions with Ig heavy chain (H) variable (V) segments or TCR‐associated Ig‐like V (TAILV) segments to form chimeric IgV‐TCR, and combine TCRδC with both Ig‐like and TCR‐like V segments to form the doubly rearranging NAR‐TCR. Activation‐induced (cytidine) deaminase‐catalyzed somatic hypermutation (SHM), typically used for B‐cell affinity maturation, also is used by TCR‐α during selection in the shark thymus presumably to salvage failing receptors. Here, we found that the use of SHM by nurse shark TCR varies depending on the particular V segment or C region used. First, SHM significantly alters alpha/delta V (TCRαδV) segments using TCR αC but not δC. Second, mutation to IgHV segments associated with TCR δC was reduced compared to mutation to TCR αδV associated with TCR αC. Mutation was present but limited in V segments of all other TCR chains including NAR‐TCR. Unexpectedly, we found preferential rearrangement of the noncanonical IgHV‐TCRδC over canonical TCR αδV‐TCRδC receptors. The differential use of SHM may reveal how activation‐induced (cytidine) deaminase targets V regions.

中文翻译：

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鲨鱼T细胞受体优先采用体细胞超突变来改变与α恒定区相关的α/δ可变片段。

除了规范的TCR和BCR，软骨鱼还装配使用各种B细胞成分的非规范TCR。例如，鲨鱼T细胞将alpha（TCR-α）或delta（TCR-δ）恒定（C）区域与Ig重链（H）可变（V）片段或与TCR相关的Ig样V（TAILV）片段相关联形成嵌合的IgV-TCR，并将TCRδC与Ig和VCR的V段结合，形成双重重排的NAR-TCR。TCR-α在鲨鱼胸腺的选择过程中也可能使用活化诱导的（胞苷）脱氨酶催化的体细胞超突变（SHM），通常用于B细胞亲和力成熟，以挽救失效的受体。在这里，我们发现护士鲨TCR对SHM的使用取决于所使用的特定V段或C区。首先，SHM使用TCRαC显着改变了alpha / delta V（TCRαδV）段，但没有改变δC。其次，与与TCRαC相关的TCRαδV的突变相比，与TCRδC相关的IgHV区段的突变减少了。存在突变，但限于所有其他TCR链的V段，包括NAR-TCR。出乎意料的是，我们发现非规范的IgHV-TCRδC优先于规范的TCRαδV-TCRδC受体重排。SHM的不同用法可能揭示了活化诱导的（胞苷）脱氨酶如何靶向V区。