Receptor revision in CD4 T cells is influenced by follicular helper T cell formation and germinal-center interactions
Abstract
The diverse T-cell receptor (TCR) repertoire is generated by selection of T cells that have undergone TCR-gene recombination during intrathymic development. This process is precisely regulated to prevent DNA damage and to minimize the escape of self-reactive T cells. Peripheral T cells with self-reactive TCRs can be neutralized by undergoing further TCR-gene rearrangements, through a process known as TCR revision. Although a potentially useful source of new TCR specificities, revision incurs the risk of off-target DNA damage. Our work demonstrates that TCR revision occurs in the germinal center, a distinct microenvironment comprising specialized cells that engage in specific interactions. Confinement to this well-regulated environment may explain how a potentially risky process can occur safely.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- April 2014
- DOI:
- 10.1073/pnas.1321803111
- Bibcode:
- 2014PNAS..111.5652H