Involvement of classical and novel protein kinase C isoforms in the response of human Vγ9Vδ2 T cells to phosphate antigens

Barbara Cipriani, Heather Knowles, Lanfen Chen, Luca Battistini, Celia F. Brosnan

Research output: Contribution to journalArticle

Abstract

Human γδ T cells expressing the Vγ9Vδ2 gene segments are activated polyclonally by phosphoantigens found on a wide variety of pathogenic organisms. After ligand exposure, Vγ9Vδ2 T cells proliferate and rapidly secrete large amounts of cytokines and chemokines that contribute to the innate immune response to these pathogens. Neither APCs nor costimulatory molecules are required. In this study we examined whether these phosphoantigens activate protein kinase Cθ (PKCθ). This novel PKC isoform is essential for Ag signaling through the αβ TCR in a costimulation-dependent fashion. The results showed that isopentenyl pyrophosphate (IPP), a soluble phospholigand released by mycobacteria, led to the rapid and persistent activation of PKCθ in γδ T cells, as determined by evidence of translocation and phosphorylation. In contrast, no ligand-dependent response was detected for PKCα/β or PKCδ. Using the inhibitors Gö6976 and rottlerin, a role for both conventional and novel PKC isoforms in IPP-induced proliferation, CD25 expression, and cytokine and chemokine production was demonstrated. Gel-shift assays indicated that the transcription factors NF-κB and AP-1 were downstream targets of PKC activation. IPP also induced the rapid and persistent phosphorylation of extracellular signal-regulated kinases 1 and 2, p38 mitogen-activated kinase, and stress-activated kinase/c-Jun N-terminal kinase, but only an inhibitor of conventional PKCs blocked these responses. We conclude that the γδ T cell response to phosphoantigens is regulated by both novel and conventional PKC isoforms, with PKCθ being more responsive to ligand stimulation and PKCα/β to growth-factor availability.

Original languageEnglish
Pages (from-to)5761-5770
Number of pages10
JournalJournal of Immunology
Volume169
Issue number10
Publication statusPublished - Nov 15 2002

    Fingerprint

ASJC Scopus subject areas

  • Immunology

Cite this