Acetylation of the Cd8 Locus by KAT6A Determines Memory T Cell Diversity
How functionally diverse populations of pathogen-specific killer T cells are generated during an immune response remains unclear. Here, we propose that fine-tuning of CD8αβ co-receptor levels via histone acetylation plays a role in lineage fate. We show that lysine acetyltransferase 6A (KAT6A) is re...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-09-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716311378 |
| _version_ | 1818550568699822080 |
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| author | Dane M. Newman Shinya Sakaguchi Aaron Lun Simon Preston Marc Pellegrini Kseniya Khamina Andreas Bergthaler Stephen L. Nutt Gordon K. Smyth Anne K. Voss Tim Thomas Wilfried Ellmeier Gabrielle T. Belz Rhys S. Allan |
| author_facet | Dane M. Newman Shinya Sakaguchi Aaron Lun Simon Preston Marc Pellegrini Kseniya Khamina Andreas Bergthaler Stephen L. Nutt Gordon K. Smyth Anne K. Voss Tim Thomas Wilfried Ellmeier Gabrielle T. Belz Rhys S. Allan |
| author_sort | Dane M. Newman |
| collection | DOAJ |
| description | How functionally diverse populations of pathogen-specific killer T cells are generated during an immune response remains unclear. Here, we propose that fine-tuning of CD8αβ co-receptor levels via histone acetylation plays a role in lineage fate. We show that lysine acetyltransferase 6A (KAT6A) is responsible for maintaining permissive Cd8 gene transcription and enabling robust effector responses during infection. KAT6A-deficient CD8+ T cells downregulated surface CD8 co-receptor expression during clonal expansion, a finding linked to reduced Cd8α transcripts and histone-H3 lysine 9 acetylation of the Cd8 locus. Loss of CD8 expression in KAT6A-deficient T cells correlated with reduced TCR signaling intensity and accelerated contraction of the effector-like memory compartment, whereas the long-lived memory compartment appeared unaffected, a result phenocopied by the removal of the Cd8 E8I enhancer element. These findings suggest a direct role of CD8αβ co-receptor expression and histone acetylation in shaping functional diversity within the cytotoxic T cell pool. |
| first_indexed | 2024-12-12T08:48:12Z |
| format | Article |
| id | doaj.art-c3c57588973b4e739d9d3cceeb66394a |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T08:48:12Z |
| publishDate | 2016-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-c3c57588973b4e739d9d3cceeb66394a2022-12-22T00:30:23ZengElsevierCell Reports2211-12472016-09-0116123311332110.1016/j.celrep.2016.08.056Acetylation of the Cd8 Locus by KAT6A Determines Memory T Cell DiversityDane M. Newman0Shinya Sakaguchi1Aaron Lun2Simon Preston3Marc Pellegrini4Kseniya Khamina5Andreas Bergthaler6Stephen L. Nutt7Gordon K. Smyth8Anne K. Voss9Tim Thomas10Wilfried Ellmeier11Gabrielle T. Belz12Rhys S. Allan13The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaDivision of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna 1090, AustriaThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, AustriaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna 1090, AustriaThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaDivision of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna 1090, AustriaThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, AustraliaHow functionally diverse populations of pathogen-specific killer T cells are generated during an immune response remains unclear. Here, we propose that fine-tuning of CD8αβ co-receptor levels via histone acetylation plays a role in lineage fate. We show that lysine acetyltransferase 6A (KAT6A) is responsible for maintaining permissive Cd8 gene transcription and enabling robust effector responses during infection. KAT6A-deficient CD8+ T cells downregulated surface CD8 co-receptor expression during clonal expansion, a finding linked to reduced Cd8α transcripts and histone-H3 lysine 9 acetylation of the Cd8 locus. Loss of CD8 expression in KAT6A-deficient T cells correlated with reduced TCR signaling intensity and accelerated contraction of the effector-like memory compartment, whereas the long-lived memory compartment appeared unaffected, a result phenocopied by the removal of the Cd8 E8I enhancer element. These findings suggest a direct role of CD8αβ co-receptor expression and histone acetylation in shaping functional diversity within the cytotoxic T cell pool.http://www.sciencedirect.com/science/article/pii/S2211124716311378T cellsvirusmemoryhistone acetylationepigenetic |
| spellingShingle | Dane M. Newman Shinya Sakaguchi Aaron Lun Simon Preston Marc Pellegrini Kseniya Khamina Andreas Bergthaler Stephen L. Nutt Gordon K. Smyth Anne K. Voss Tim Thomas Wilfried Ellmeier Gabrielle T. Belz Rhys S. Allan Acetylation of the Cd8 Locus by KAT6A Determines Memory T Cell Diversity Cell Reports T cells virus memory histone acetylation epigenetic |
| title | Acetylation of the Cd8 Locus by KAT6A Determines Memory T Cell Diversity |
| title_full | Acetylation of the Cd8 Locus by KAT6A Determines Memory T Cell Diversity |
| title_fullStr | Acetylation of the Cd8 Locus by KAT6A Determines Memory T Cell Diversity |
| title_full_unstemmed | Acetylation of the Cd8 Locus by KAT6A Determines Memory T Cell Diversity |
| title_short | Acetylation of the Cd8 Locus by KAT6A Determines Memory T Cell Diversity |
| title_sort | acetylation of the cd8 locus by kat6a determines memory t cell diversity |
| topic | T cells virus memory histone acetylation epigenetic |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716311378 |
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