The dominant role of CD8+ dendritic cells in cross-presentation is not dictated by antigen capture.
Mouse spleens contain three populations of conventional (CD11c(high)) dendritic cells (DCs) that play distinct functions. The CD8(+) DC are unique in that they can present exogenous antigens on their MHC class I molecules, a process known as cross-presentation. It is unclear whether this special ability is because only the CD8(+) DC can capture the antigens used in cross-presentation assays, or because this is the only DC population that possesses specialized machinery for cross-presentation. To solve this important question we examined the splenic DC subsets for their ability to both present via MHC class II molecules and cross-present via MHC class I using four different forms of the model antigen ovalbumin (OVA). These forms include a cell-associated form, a soluble form, OVA expressed in bacteria, or OVA bound to latex beads. With the exception of bacterial antigen, which was poorly cross-presented by all DC, all antigenic forms were cross-presented much more efficiently by the CD8(+) DC. This pattern could not be attributed simply to a difference in antigen capture because all DC subsets presented the antigen via MHC class II. Indeed, direct assessments of endocytosis showed that CD8(+) and CD8(-) DC captured comparable amounts of soluble and bead-associated antigen, yet only the CD8(+) DC cross-presented these antigenic forms. Our results indicate that cross-presentation requires specialized machinery that is expressed by CD8(+) DC but largely absent from CD8(-) DC. This conclusion has important implications for the design of vaccination strategies based on antigen targeting to DC.
Schnorrer
Petra
P
Immunology Division and Cooperative Research Centre for Vaccine Technology, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
Behrens
Georg M N
GM
Wilson
Nicholas S
NS
Pooley
Joanne L
JL
Smith
Christopher M
CM
El-Sukkari
Dima
D
Davey
Gayle
G
Kupresanin
Fiona
F
Li
Ming
M
Maraskovsky
Eugene
E
Belz
Gabrielle T
GT
Carbone
Francis R
FR
Shortman
Ken
K
Heath
William R
WR
Villadangos
Jose A
JA
D000818:Animals; D000941:Antigens / Q000378:metabolism*; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000096:biosynthesis*; D002478:Cells, Cultured; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D007840:Latex; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008863:Microspheres; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D000941:Antigens; D000942:Antigens, Bacterial; D016827:CD8 Antigens; D007840:Latex; D010047:Ovalbumin