Nurse shark T‐cell receptors employ somatic hypermutation preferentially to alter alpha/delta variable segments associated with alpha constant region
| Autor: | Jeannine A. Ott, Jenna Harrison, Michael F. Criscitiello, Martin F. Flajnik |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Gene Rearrangement delta-Chain T-Cell Antigen Receptor Immunology Somatic hypermutation chemical and pharmacologic phenomena medicine.disease_cause Article Affinity maturation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cytidine Deaminase medicine Animals Immunology and Allergy Mutation biology T-cell receptor breakpoint cluster region hemic and immune systems Cytidine biology.organism_classification Delta-v (physics) Cell biology 030104 developmental biology chemistry Sharks Somatic Hypermutation Immunoglobulin Nurse shark Gene Rearrangement alpha-Chain T-Cell Antigen Receptor Immunoglobulin Heavy Chains 030215 immunology |
| Zdroj: | Eur J Immunol |
| ISSN: | 1521-4141 0014-2980 |
| DOI: | 10.1002/eji.201948495 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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