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.
Moor
Rebecca J
RJ
Division of Immunology and Infectious Diseases, Queensland Institute of Medical Research, Herston, Queensland, Australia.
Morrison
Leanne E
LE
Moss
Denis J
DJ
Tscharke
David C
DC
D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002277:Carcinoma / Q000276:immunology; D018929:Cell Culture Techniques; D002469:Cell Separation; D002478:Cells, Cultured; D005434:Flow Cytometry / Q000379:methods*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000032:analysis* / Q000378:metabolism; D052119:Lysosomal-Associated Membrane Protein 2 / Q000032:analysis* / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000276:immunology; D013379:Substrate Specificity
D016056:Immunodominant Epitopes; D052118:Lysosomal-Associated Membrane Protein 1; D052119:Lysosomal-Associated Membrane Protein 2