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Differential requirements for CTL generation by novel immunostimulants: APC tropism, use of the TAP-independent processing pathway, and dependency on CD80/CD86 costimulation

Differential requirements for CTL generation by novel immunostimulants: APC tropism, use of the TAP-independent processing pathway, and dependency on CD80/CD86 costimulation
Differential requirements for CTL generation by novel immunostimulants: APC tropism, use of the TAP-independent processing pathway, and dependency on CD80/CD86 costimulation
A major drawback of subunit vaccines is their inability to generate cytolytic T lymphocytes (CTL), a deficit attributed to segregation of the class I and class II antigen-processing pathways. We sought to understand processes involved in CTL induction by three proprietary adjuvants: Tomatine, PROVAX(TM), and a synthesized glycolipid (Glc-N-(8/16), Glycolipid). We used in vivo models to investigate antigen uptake, macrophage involvement, TAP-independent processing, and costimulatory molecule dependencies. Glycolipid required splenic and lymph node macrophages, whereas Tomatine generated CTL independently of either macrophage population. In contrast, PROVAX(TM), showed partial macrophage requirements. Immunized TAP knockout mice revealed that ovalbumin (OVA)-Tomatine and OVA-PROVAX(TM), but not OVA-Glycolipid, generate class I-peptide complexes. All three immunostimulants also elicited CD86-dependent T(H)1 cytokine responses.
adjuvant, costimulation, tomatine cytotoxic t-cells, class-i molecules, spleen dendritic cells, antigenpresentation, soluble-protein, endoplasmic-reticulum, cytokineproduction, antitumor immunity, macrophages, responses
3775-3788
Sheikh, Nadeem A.
3219075d-2364-4f00-aeb9-1d90f8cd0d36
van Rooijen, Nico
a9f3fc94-192d-4e2d-b662-765bd778bc55
Rajananthanan, Palasingam
9075a018-e584-4e1f-92e5-03ebf383e859
Hariharan, Kandasamy
4cb3c68f-ecf8-4cfc-8eb0-7f0808ff4b2b
Yang, Ya-Wum
454e93d4-b69a-478f-9bbc-1d0a075f9b94
Morrow, W. John W.
5b20d0d4-e9c5-498b-a34b-a942407d229b
Sheikh, Nadeem A.
3219075d-2364-4f00-aeb9-1d90f8cd0d36
van Rooijen, Nico
a9f3fc94-192d-4e2d-b662-765bd778bc55
Rajananthanan, Palasingam
9075a018-e584-4e1f-92e5-03ebf383e859
Hariharan, Kandasamy
4cb3c68f-ecf8-4cfc-8eb0-7f0808ff4b2b
Yang, Ya-Wum
454e93d4-b69a-478f-9bbc-1d0a075f9b94
Morrow, W. John W.
5b20d0d4-e9c5-498b-a34b-a942407d229b

Sheikh, Nadeem A., van Rooijen, Nico, Rajananthanan, Palasingam, Hariharan, Kandasamy, Yang, Ya-Wum and Morrow, W. John W. (2003) Differential requirements for CTL generation by novel immunostimulants: APC tropism, use of the TAP-independent processing pathway, and dependency on CD80/CD86 costimulation. Vaccine, 21 (25-26), 3775-3788. (doi:10.1016/S0264-410X(03)00314-1).

Record type: Article

Abstract

A major drawback of subunit vaccines is their inability to generate cytolytic T lymphocytes (CTL), a deficit attributed to segregation of the class I and class II antigen-processing pathways. We sought to understand processes involved in CTL induction by three proprietary adjuvants: Tomatine, PROVAX(TM), and a synthesized glycolipid (Glc-N-(8/16), Glycolipid). We used in vivo models to investigate antigen uptake, macrophage involvement, TAP-independent processing, and costimulatory molecule dependencies. Glycolipid required splenic and lymph node macrophages, whereas Tomatine generated CTL independently of either macrophage population. In contrast, PROVAX(TM), showed partial macrophage requirements. Immunized TAP knockout mice revealed that ovalbumin (OVA)-Tomatine and OVA-PROVAX(TM), but not OVA-Glycolipid, generate class I-peptide complexes. All three immunostimulants also elicited CD86-dependent T(H)1 cytokine responses.

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More information

Published date: 8 September 2003
Keywords: adjuvant, costimulation, tomatine cytotoxic t-cells, class-i molecules, spleen dendritic cells, antigenpresentation, soluble-protein, endoplasmic-reticulum, cytokineproduction, antitumor immunity, macrophages, responses

Identifiers

Local EPrints ID: 20081
URI: http://eprints.soton.ac.uk/id/eprint/20081
PURE UUID: fb9310fa-f176-4f09-9869-b60e8f8705a6
ORCID for Nadeem A. Sheikh: ORCID iD orcid.org/0000-0001-8304-0742

Catalogue record

Date deposited: 24 Feb 2006
Last modified: 16 Mar 2024 02:44

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Contributors

Author: Nico van Rooijen
Author: Palasingam Rajananthanan
Author: Kandasamy Hariharan
Author: Ya-Wum Yang
Author: W. John W. Morrow

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