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CD11c provides an effective immunotarget for the generation of both CD4 and CD8 T cell responses

CD11c provides an effective immunotarget for the generation of both CD4 and CD8 T cell responses
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.

0014-2980
2263 -2273
Castro, Fernanda V.V.
907b15df-0007-4835-9253-b32af066f04d
Tutt, Alison L.
46ce577b-aea1-412d-84ea-fc4dab794469
White, Ann L.
dd7e96b0-c826-4495-a2bc-4e3bcde699de
Teeling, Jessica L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
James, Sonya
764c80e3-5bea-4b34-a871-b43f87ef97b0
French, Ruth R.
a95ea7a1-7aeb-4c20-998e-fde663613fd1
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Castro, Fernanda V.V.
907b15df-0007-4835-9253-b32af066f04d
Tutt, Alison L.
46ce577b-aea1-412d-84ea-fc4dab794469
White, Ann L.
dd7e96b0-c826-4495-a2bc-4e3bcde699de
Teeling, Jessica L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
James, Sonya
764c80e3-5bea-4b34-a871-b43f87ef97b0
French, Ruth R.
a95ea7a1-7aeb-4c20-998e-fde663613fd1
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded

Castro, Fernanda V.V., Tutt, Alison L., White, Ann L., Teeling, Jessica L., James, Sonya, French, Ruth R. and Glennie, Martin J. (2008) CD11c provides an effective immunotarget for the generation of both CD4 and CD8 T cell responses. European Journal of Immunology, 38 (8), 2263 -2273. (doi:10.1002/eji.200838302). (PMID:18651710)

Record type: Article

Abstract

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.

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Published date: 2008

Identifiers

Local EPrints ID: 79345
URI: https://eprints.soton.ac.uk/id/eprint/79345
ISSN: 0014-2980
PURE UUID: 20088704-f275-4357-85f2-f459b1703a73
ORCID for Jessica L. Teeling: ORCID iD orcid.org/0000-0003-4004-7391

Catalogue record

Date deposited: 15 Mar 2010
Last modified: 19 Nov 2019 01:47

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