Somatic hypermutation of TCR contributes to thymic positive selection in sharks Academic Article uri icon

abstract

  • Abstract In mammals and probably all vertebrates, receptor editing of TCR alpha genes enhances immature T cell positive selection over a three-day interval in the thymic cortex. Surprisingly we found extensive somatic hypermutation (SHM) operating at the TCR locus in the nurse shark thymus, implying that SHM contributes to receptor modifications that enhance positive selection. We analyzed mutation in TCR families of clones with the same VJ rearrangement. Additionally, in situ hybridization showed the strongest activation-induced cytidine deaminase (AID) expression in the central thymic cortex and bordering the corticomedullary junction. The frequency of mutation at TCR was as high as that seen at B cell receptor (BCR) loci in sharks and mammals. Complementarity determining regions (CDRs) accumulated significantly more mutations than framework regions (FWs), and significantly more mutations in CDRs resulted in amino acid replacement than in silent mutation. We saw a preference for transition mutations as well as a strong bias toward G:C substitutions within AID hotspots, especially within CDR regions. We suggest that TCR utilizes SHM to boost positive selection and perhaps to broaden diversification of the T cell repertoire in sharks, the first reported use of this process in thymic diversification in vertebrates.

published proceedings

  • The Journal of Immunology

author list (cited authors)

  • Ott, J. A., Castro, C., Deiss, T., Ota, Y., Flajnik, M. F., & Criscitiello, M. F.

citation count

  • 0

complete list of authors

  • Ott, Jeannine A||Castro, Caitlin||Deiss, Thaddeus||Ota, Yuko||Flajnik, Martin F||Criscitiello, Michael F

publication date

  • May 2018