Direct stimulation of T cells by membrane vesicles from antigen-presenting cells.
Activation of naïve T cells generally requires T cell receptor-mediated contact with MHC-bound peptides on viable antigen-presenting cells such as dendritic cells (DC). Here evidence is presented that dissociated cell membrane fragments from a DC line can be used as an effective substitute for viable DC. Ultracentrifuged material derived from sonicates of IFN-gamma-matured DC is enriched in small membrane vesicles that closely resemble exosomes. When complexed with MHC class I-restricted specific peptide, vesicles from DC sonicates generate strong responses by purified naïve CD8(+) cells in vitro in the absence of normal antigen-presenting cells and can also efficiently prime T cells for tumor rejection in vivo. Both in terms of total yields from DC and relative immunogenicity, membrane vesicles from DC sonicates are much more effective than classic exosomes and may be a valuable tool for tumor immunotherapy.
Kovar
Marek
M
The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Boyman
Onur
O
Shen
Xuefei
X
Hwang
Inkyu
I
Kohler
Rachel
R
Sprent
Jonathan
J
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology*; D022162:Cytoplasmic Vesicles / Q000276:immunology*; D005805:Genes, MHC Class I; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D010455:Peptides