Differential requirements for CTL generation by novel immunostimulants: APC tropism, use of the TAP-independent processing pathway, and dependency on CD80/CD86 costimulation
Sheikh, Nadeem A., Attard, George S., 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)
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Official URL: http://dx.doi.org/10.1016/S0264-410X(03)00314-1
Description/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.
| Item Type: | Article |
|---|---|
| ISSN: | 0264-410 (print) |
| Uncontrolled Keywords: | adjuvant, costimulation, tomatine cytotoxic t-cells, class-i molecules, spleen dendritic cells, antigenpresentation, soluble-protein, endoplasmic-reticulum, cytokineproduction, antitumor immunity, macrophages, responses |
| Related URLs: | http://www.ncbi.nlm.nih.gov/en...med_docsum http://dx.doi.org/10.1016/S026...03)00314-1 |
| Subjects: | Q Science > QD Chemistry Q Science > QR Microbiology > QR180 Immunology |
| Divisions: | University Structure - Pre August 2011 > School of Chemistry |
| ePrint ID: | 20081 |
| URI: | http://eprints.soton.ac.uk/id/eprint/20081 |
| Deposited On: | 24 Feb 2006 |
| Last Modified: | 01 Jun 2011 00:31 |
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