Oct1 and OCA-B are selectively required for CD4 memory T cell function

Arvind Shakya, Alon Goren, Alex Shalek, Cody N German, Jeremy Snook, Vijay K Kuchroo, Nir Yosef, Raymond C Chan, Aviv Regev, Matthew A Williams, Dean Tantin

Research output: Contribution to journalArticlepeer-review

Abstract

Epigenetic changes are crucial for the generation of immunological memory. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic states offers a potential method of enhancing memory. Yet the transcription factors that regulate these processes are poorly defined. We find that the transcription factor Oct1 and its cofactor OCA-B are selectively required for the in vivo generation of CD4+ memory T cells. More importantly, the memory cells that are formed do not respond properly to antigen reencounter. In vitro, both proteins are required to maintain a poised state at the Il2 target locus in resting but previously stimulated CD4+ T cells. OCA-B is also required for the robust reexpression of multiple other genes including Ifng. ChIPseq identifies ~50 differentially expressed direct Oct1 and OCA-B targets. We identify an underlying mechanism involving OCA-B recruitment of the histone lysine demethylase Jmjd1a to targets such as Il2, Ifng, and Zbtb32. The findings pinpoint Oct1 and OCA-B as central mediators of CD4+ T cell memory.

Original languageEnglish
Pages (from-to)2115-2131
Number of pages17
JournalJournal of Experimental Medicine
Volume212
Issue number12
Early online date19 Oct 2015
DOIs
StatePublished - 16 Nov 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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