Antibody responses initiated by Clec9A-bearing dendritic cells in normal and Batf3(-/-) mice.
Injection of antigens coupled to antibodies against the dendritic cell (DC) surface molecule Clec9A has been shown to produce strongly enhanced antibody responses even without co-administration of adjuvants, via antigen presentation by DC on MHC class II and consequent production of follicular helper T cells. A series of mutant mice were tested to determine the DC subtypes responsible for this MHC II presentation of targeted antigen, compared to presentation of antigen on MHC I. A new clec9A null mouse was developed; these mice did not give enhanced antibody production, confirming the response was dependent on Clec9A-expressing DC. However targeting of antigen to Clec9A in batf3 null mice produced enhanced antibody responses despite the marked reduction in CD8(+) DC, the major Clec9A-expressing DC subtype. This was shown to be dependent on efficient MHC II presentation by minor Clec9A-expressing DC subtypes in the environment of the Batf3(-/-) mice, namely early cells of the CD8 DC lineage and the plasmacytoid-related CD8(+) DC subset, but not by plasmacytoid cells themselves. However in normal mice most MHC II presentation of the Clec9A-targeted antigen was by the major CD8(+) DC population, the DC also responsible for presentation on MHC I.
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.
Irina
I
Caminschi
David
D
Vremec
Fatma
F
Ahmet
Mireille H
MH
Lahoud
Jose A
JA
Villadangos
Kenneth M
KM
Murphy
William R
WR
Heath
Ken
K
Shortman
D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D017951:Antigen Presentation / Q000276:immunology; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D000099185:Interferon Regulatory Factor-8
D050976:Basic-Leucine Zipper Transcription Factors; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D050835:Interferon Regulatory Factors; D037181:Lectins, C-Type; D010047:Ovalbumin; D011971:Receptors, Immunologic; D012097:Repressor Proteins; D000099185:Interferon Regulatory Factor-8; C529914:Clec9a protein, mouse; C533289:SNFT protein, mouse