Somatic hypermutation of T cell receptor α chain contributes to selection in nurse shark thymus
- Texas A&M University, United States
- University of Maryland, United States
Abstract
Since the discovery of the T cell receptor (TcR), immunologists have assigned somatic hypermutation (SHM) as a mechanism employed solely by B cells to diversify their antigen receptors. Remarkably, we found SHM acting in the thymus on α chain locus of shark TcR. SHM in developing shark T cells likely is catalyzed by activation-induced cytidine deaminase (AID) and results in both point and tandem mutations that accumulate non-conservative amino acid replacements within complementarity-determining regions (CDRs). Mutation frequency at TcRα was as high as that seen at B cell receptor loci (BcR) in sharks and mammals, and the mechanism of SHM shares unique characteristics first detected at shark BcR loci. Additionally, fluorescence in situ hybridization showed the strongest AID expression in thymic corticomedullary junction and medulla. We suggest that TcRα utilizes SHM to broaden diversification of the primary αβ T cell repertoire in sharks, the first reported use in vertebrates.
Data availability
T cell receptor sequences have been deposited in Genbank of NCBI.Alpha KY189332-KY189354 and KY366469-KY355487;Beta KY351708-KY366487;Gamma KY351639-KY351707;Delta KY346705-KY346816
Article and author information
Author details
Michael F Criscitiello
Funding
National Science Foundation (IOS 1257829)
- Michael F Criscitiello
National Institute of Allergy and Infectious Diseases (R01OD0549)
- Martin F Flajnik
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: These studies were carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Animal Care and Use Committees at Texas A&M University and University of Maryland School of Medicine. Experiments in the Criscitiello lab were performed under Texas A&M University Institutional Biosafety Committee permit IBC 2014-293 and Animal Use Protocol 2015-0374.
Copyright
© 2018, Ott et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Somatic hypermutation of T cell receptor α chain contributes to selection in nurse shark thymus
eLife 7:e28477.
https://doi.org/10.7554/eLife.28477
