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For example, shark T\u00a0cells associate alpha (TCR\u2010\u03b1) or delta (TCR\u2010\u03b4) constant (C) regions with Ig heavy chain (H) variable (V) segments or TCR\u2010associated Ig\u2010like V (TAILV) segments to form chimeric IgV\u2010TCR, and combine TCR\u03b4C with both Ig\u2010like and TCR\u2010like V segments to form the doubly rearranging NAR\u2010TCR. Activation\u2010induced (cytidine) deaminase\u2010catalyzed somatic hypermutation (SHM), typically used for B\u2010cell affinity maturation, also is used by TCR\u2010\u03b1 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 (TCR\u03b1\u03b4V) segments using TCR \u03b1C but not \u03b4C. Second, mutation to IgHV segments associated with TCR \u03b4C was reduced compared to mutation to TCR \u03b1\u03b4V associated with TCR \u03b1C. Mutation was present but limited in V segments of all other TCR chains including NAR\u2010TCR. Unexpectedly, we found preferential rearrangement of the noncanonical IgHV\u2010TCR\u03b4C over canonical TCR \u03b1\u03b4V\u2010TCR\u03b4C receptors. The differential use of SHM may reveal how activation\u2010induced (cytidine) deaminase targets V regions.<\/jats:p>","DOI":"10.1002\/eji.201948495","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T03:23:56Z","timestamp":1588130636000},"page":"1307-1320","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Nurse shark T\u2010cell receptors employ somatic hypermutation preferentially to alter alpha\/delta variable segments associated with alpha constant region"],"prefix":"10.1002","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3537-8631","authenticated-orcid":false,"given":"Jeannine A.","family":"Ott","sequence":"first","affiliation":[{"name":"Comparative Immunogenetics Laboratory Department of Veterinary Pathobiology College of Veterinary Medicine and Biomedical Sciences Texas A&amp;M University  College Station TX 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