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Prolonged antigen survival and cytosolic export in cross-presenting human γδ T cells

Human blood Vγ9Vδ2 T cells respond to signals from microbes and tumors and subsequently differentiate into professional antigen-presenting cells (γδ T-APCs) for induction of CD4⁺ and CD8⁺ T cell responses. γδ T-APCs readily take up and degrade exogenous soluble protein for peptide loading on MHC I,...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2010-05, Vol.107 (19), p.8730-8735
Main Authors: Meuter, Simone, Eberl, Matthias, Moser, Bernhard
Format: Article
Language:English
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Summary:Human blood Vγ9Vδ2 T cells respond to signals from microbes and tumors and subsequently differentiate into professional antigen-presenting cells (γδ T-APCs) for induction of CD4⁺ and CD8⁺ T cell responses. γδ T-APCs readily take up and degrade exogenous soluble protein for peptide loading on MHC I, in a process termed antigen cross-presentation. The mechanisms underlying antigen cross-presentation are ill-defined, most notably in human dendritic cells (DCs), and no study has addressed this process in γδ T-APCs. Here we show that intracellular protein degradation and endosomal acidification were significantly delayed in γδ T-APCs compared with human monocyte-derived DCs (moDCs). Such conditions are known to favor antigen cross-presentation. In both γδ T-APCs and moDCs, internalized antigen was transported across insulin-regulated aminopeptidase (IRAP)-positive early and late endosomes; however, and in contrast to various human DC subsets, γδ T-APCs efficiently translocated soluble antigen into the cytosol for processing via the cytosolic proteasome-dependent cross-presentation pathway. Of note, γδ T-APCs cross-presented influenza antigen derived from virus-infected cells and from free virus particles. The robust cross-presentation capability appears to be a hallmark of γδ T-APCs and underscores their potential application in cellular immunotherapy.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1002769107