EF hand domain family member D2 is required for T cell cytotoxicity

Michael Peled, Matthew A. Dragovich, Kieran Adam, Marianne Strazza, Anna S. Tocheva, Irving E. Vega, Adam Mor

Research output: Contribution to journalArticlepeer-review

Abstract

Programmed cell death 1 (PD-1) is a major coinhibitory receptor and a member of the immunological synapse (IS). To uncover proteins that regulate PD-1 recruitment to the IS, we searched for cytoskeleton-related proteins that also interact with PD-1 using affinity purification mass spectrometry. Among these proteins, EF hand domain family member D2 (EFHD2), a calcium binding adaptor protein, was functionally and mechanistically analyzed for its contribution to PD-1 signaling. EFHD2 was required for PD-1 to inhibit cytokine secretion, proliferation, and adhesion of human T cells. Interestingly, EFHD2 was also required for human T cell-mediated cytotoxicity and for mounting an antitumor immune response in a syngeneic murine tumor model. Mechanistically, EFHD2 contributed to IS stability, lytic vesicles trafficking, and granzyme B secretion. Altogether, EFHD2 is an important regulator of T cell cytotoxicity and further studies should evaluate its role in T cell-mediated inflammation.

Original languageEnglish
Pages (from-to)2812-2823
Number of pages12
JournalJournal of Immunology
Volume201
Issue number9
DOIs
StatePublished - 1 Nov 2018
Externally publishedYes

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