Targeting antigen to MHC class II molecules promotes efficient cross-presentation and enhances immunotherapy.
An efficient pathway of cross-presentation common to a range of dendritic cell (DC) populations was identified by targeting Ag to MHC class II molecules. This finding was achieved by conjugating Ag to M1, which is a modified version of the superantigen streptococcal mitogenic exotoxin Z-2 that binds to MHC class II molecules but cannot directly stimulate T cells. M1 conjugates were efficiently presented to CD4(+) and CD8(+) T cells by bone marrow-derived DC and Langerhans cells in vitro. Whereas nonconjugated Ag was preferentially cross-presented by splenic CD8alpha(+) DC in vivo, M1-conjugated Ag was cross-presented by all dendritic subtypes assessed. Potent effector T cell responses with antitumor activity were elicited when M1 conjugates were injected together with an adjuvant. This method of Ag delivery has significant potential in therapeutic applications.
Dickgreber
Nina
N
Malaghan Institute of Medical Research, Wellington, New Zealand.
Stoitzner
Patrizia
P
Bai
Yan
Y
Price
Kylie M
KM
Farrand
Kathryn J
KJ
Manning
Kristy
K
Angel
Catherine E
CE
Dunbar
P Rod
PR
Ronchese
Franca
F
Fraser
John D
JD
Bäckström
B Thomas
BT
Hermans
Ian F
IF
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D001427:Bacterial Toxins / Q000008:administration & dosage* / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005098:Exotoxins / Q000008:administration & dosage* / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D008024:Ligands; D008546:Melanoma, Experimental / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000276:immunology; D018089:Superantigens / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism
D001427:Bacterial Toxins; D019496:Cancer Vaccines; D005098:Exotoxins; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D018089:Superantigens; C107894:mitogenic exotoxin Z protein, Streptococcus