The dendritic cell subtype-restricted C-type lectin Clec9A is a target for vaccine enhancement.
A novel dendritic cell (DC)-restricted molecule, Clec9A, was identified by gene expression profiling of mouse DC subtypes. Based on sequence similarity, a human ortholog was identified. Clec9A encodes a type II membrane protein with a single extracellular C-type lectin domain. Both the mouse Clec9A and human CLEC9A were cloned and expressed, and monoclonal antibodies (mAbs) against each were generated. Surface staining revealed that Clec9A was selective for mouse DCs and was restricted to the CD8(+) conventional DC and plasmacytoid DC subtypes. A subset of human blood DCs also expressed CLEC9A. A single injection of mice with a mAb against Clec9A, which targets antigens (Ags) to the DCs, produced a striking enhancement of antibody responses in the absence of added adjuvants or danger signals, even in mice lacking Toll-like receptor signaling pathways. Such targeting also enhanced CD4 and CD8 T-cell responses. Thus, Clec9A serves as a new marker to distinguish subtypes of both mouse and human DCs. Furthermore, targeting Ags to DCs with antibodies to Clec9A is a promising strategy to enhance the efficiency of vaccines, even in the absence of adjuvants.
Caminschi
Irina
I
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Proietto
Anna I
AI
Ahmet
Fatma
F
Kitsoulis
Susie
S
Shin Teh
Joo
J
Lo
Jennifer C Y
JC
Rizzitelli
Alexandra
A
Wu
Li
L
Vremec
David
D
van Dommelen
Serani L H
SL
Campbell
Ian K
IK
Maraskovsky
Eugene
E
Braley
Hal
H
Davey
Gayle M
GM
Mottram
Patricia
P
van de Velde
Nicholas
N
Jensen
Kent
K
Lew
Andrew M
AM
Wright
Mark D
MD
Heath
William R
WR
Shortman
Ken
K
Lahoud
Mireille H
MH
D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014612:Vaccines / Q000737:chemistry / Q000378:metabolism
D037181:Lectins, C-Type; D014612:Vaccines