September 22, 2019  |  

Somatic hypermutation of T cell receptor a chain contributes to selection in nurse shark thymus.

Authors: Ott, Jeannine A and Castro, Caitlin D and Deiss, Thaddeus C and Ohta, Yuko and Flajnik, Martin F and Criscitiello, Michael F

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 a 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 TcRa 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 TcRa utilizes SHM to broaden diversification of the primary aß T cell repertoire in sharks, the first reported use in vertebrates.© 2018, Ott et al.

Journal: eLife
DOI: 10.7554/eLife.28477
Year: 2018

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