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

Meuter, Simone, Eberl, Matthias ORCID: https://orcid.org/0000-0002-9390-5348 and Moser, Bernhard ORCID: https://orcid.org/0000-0002-4354-4572 2010. Prolonged antigen survival and cytosolic export in cross-presenting human γδ T cells. Proceedings of the National Academy of Sciences of the United States of America 107 (19) , pp. 8730-8735. 10.1073/pnas.1002769107

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR180 Immunology R Medicine > RM Therapeutics. Pharmacology R Medicine > RZ Other systems of medicine
Uncontrolled Keywords:	antigen cross-presentation; dendritic cells; γ/δ T cells; influenza virus
Publisher:	National Academy of Sciences
ISSN:	0027-8424
Last Modified:	19 Oct 2022 10:41
URI:	https://orca.cardiff.ac.uk/id/eprint/25204

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