Use of CD107-based cell sorting ex vivo to enrich subdominant CD8 ⁺ T cells in culture

CD8⁺ T lymphocytes are key effectors in the control of viral diseases and some tumours. In general, the majority of CD8⁺ T cells recognize a few immunodominant epitopes, but in some circumstances, subdominant specificities may be more relevant as targets for vaccines or immunotherapy. Epstein-Barr virus (EBV)-associated cancers are an example where knowledge of subdominant-specific CD8⁺ T cells is important because the immunodominant EBV proteins are not expressed in these cancers. We have developed a live-cell sorting method based on CD107 detection to remove CD8 ⁺ T cells recognising dominant EBV epitopes and show that this allows enrichment of subdominant-specific CD8⁺ T cells in subsequent cultures. This work shows that immunodomination in vitro suppresses the outgrowth of subdominant-specific CD8⁺ T cells in culture. The method may have broad applications for finding subdominant targets for immunotherapy and vaccines, and the principle suggests a means of improving subdominant CD8⁺ T-cell cultures grown for immunotherapy.