Somatic hypermutation of T cell receptor α chain contributes to selection in nurse shark thymus
PublishereLife Sciences Publications Ltd
MetadataShow full item record
Other TitlesSomatic hypermutation of T cell receptor α chain contributes to selection in nurse shark thymus
AbstractSince 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. Copyright Ott et al.
SponsorsNational Science Foundation
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85050694223&doi=10.7554%2feLife.28477&partnerID=40&md5=f9ac96420039ed1f8dee194a3929cf2c; http://hdl.handle.net/10713/9162
- Nurse Shark T Cell Receptors Employ Somatic Hypermutation Preferentially to Alter Alpha/Delta Variable Segments Associated with Alpha Constant Region.
- Authors: Ott JA, Harrison J, Flajnik MF, Criscitiello MF
- Issue date: 2020 Apr 29
- Somatic hypermutation of TCR γ V genes in the sandbar shark.
- Authors: Chen H, Bernstein H, Ranganathan P, Schluter SF
- Issue date: 2012 May
- T Cell Receptor Alpha Chain Genes in the Teleost Ballan Wrasse <i>(Labrus bergylta)</i> Are Subjected to Somatic Hypermutation.
- Authors: Bilal S, Lie KK, Sæle Ø, Hordvik I
- Issue date: 2018
- Somatic hypermutation of the new antigen receptor gene (NAR) in the nurse shark does not generate the repertoire: possible role in antigen-driven reactions in the absence of germinal centers.
- Authors: Diaz M, Greenberg AS, Flajnik MF
- Issue date: 1998 Nov 24
- A target selection of somatic hypermutations is regulated similarly between T and B cells upon activation-induced cytidine deaminase expression.
- Authors: Kotani A, Okazaki IM, Muramatsu M, Kinoshita K, Begum NA, Nakajima T, Saito H, Honjo T
- Issue date: 2005 Mar 22