OmpA targets dendritic cells, induces their maturation and delivers antigen into the MHC class I presentation pathway.
We analyzed the interaction between a bacterial cell wall protein and dendritic cells (DCs). Outer membrane protein A from Klebsiella pneumoniae (kpOmpA) specifically bound to professional antigen presenting cells and was endocytosed by immature DCs via a receptor-dependent mechanism. kpOmpA signaled through Toll-like receptor 2, induced DCs to produce interleukin 12 and induced maturation of DCs. Whole antigen that was coupled to kpOmpA and injected into mice was taken up by DCs and delivered to the conventional cytosolic MHC class I presentation pathway. kpOmpA also primed antigen-specific CD8+ CTLs in the absence of CD4+ T cell help or adjuvant and elicited therapeutic immunity to antigen-expressing tumors. Thus, OmpA belongs to a class of proteins that are able to elicit CTL responses to exogenous antigen.
Jeannin
P
P
Centre d'Immunologie Pierre Fabre, 5, Avenue Napoléon III, F-74164 Saint-Julien en Genevois, France. pascale.jeannin@pierre-fabre.com
Renno
T
T
Goetsch
L
L
Miconnet
I
I
Aubry
J P
JP
Delneste
Y
Y
Herbault
N
N
Baussant
T
T
Magistrelli
G
G
Soulas
C
C
Romero
P
P
Cerottini
J C
JC
Bonnefoy
J Y
JY
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D029721:Drosophila Proteins; D004705:Endocytosis; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007711:Klebsiella pneumoniae / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D010047:Ovalbumin / Q000276:immunology; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
D001425:Bacterial Outer Membrane Proteins; D029721:Drosophila Proteins; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; C078167:OMPA outer membrane proteins; D010047:Ovalbumin