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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 107; no. 19; pp. 8730 - 8735
• Main Authors: Meuter, Simone, Eberl, Matthias, Moser, Bernhard
• Format: Journal Article
• Language: English
• Published: National Academy of Sciences 11.05.2010; National Acad Sciences
• Subjects: acidification; aminopeptidases; Antigens; Apoptosis; Biological Sciences; CD8-positive T-lymphocytes; Cell lines; Cross priming; Cytosol; Dendritic cells; Endosomes; HEK293 cells; humans; immunotherapy; influenza; microorganisms; neoplasms; protein degradation; T lymphocytes; virion; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1002769107

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.