CD11c provides an effective immunotarget for the generation of both CD4 and CD8 T cell responses.
The magnitude and quality of T cell responses generated when Ag is targeted to receptors on DC is influenced by both the specific receptor targeted and its distribution among DC subsets. Here we examine the targeting of the model Ag OVA to potential DC targets, including CD11c, CD205, MHC class II, CD40, TLR2 and FcgammaRII/III, using a panel of (Fab' x OVA) conjugates. In vitro studies identified CD11c, CD205 and MHC class II as superior and comparably effective immunotargets for the delivery of OVA to APC for presentation to T cells. In vivo studies, however, showed a marked advantage of targeting Ag to CD11c for both CD4 (OT-II) and CD8 (OT-I) responses, with robust stimulation after a single, low dose (equivalent to 0.5 microg OVA); in contrast, (anti-CD205 x OVA) and (anti-MHC class II x OVA) resulted in markedly less proliferation of both OT-I and OT-II cells. Biodistribution and immunohistochemical studies suggest that the exceptional ability of CD11c to capture Ag in lymphoid tissues may, at least partially, explain its ability to promote T cell responses. These results suggest that targeting antigen via CD11c offers a previously unappreciated strategy for vaccine development which, unlike most targets, delivers robust responses of both CD4 and CD8 T cells.
Castro
Fernanda V V
FV
Tenovus Research Laboratory, Cancer Sciences Division, Southampton University School of Medicine, Southampton, UK.
Tutt
Alison L
AL
White
Ann L
AL
Teeling
Jessica L
JL
James
Sonya
S
French
Ruth R
RR
Glennie
Martin J
MJ
D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000502:physiology; D039521:CD11c Antigen / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007114:Immunization; D037181:Lectins, C-Type / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D010047:Ovalbumin / Q000276:immunology; D011956:Receptors, Cell Surface / Q000502:physiology; D013154:Spleen / Q000276:immunology
D015703:Antigens, CD; D039521:CD11c Antigen; C093569:DEC-205 receptor; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D010047:Ovalbumin