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A novel method to identify and characterise peptide mimotopes of heat shock protein 70-associated antigens
Doherty, Derek; Arnaiz, Blanca; Madrigal-Estebas, Laura; Todryk, Stephen; James, Tharappel C; Bond, Ursula
The heat shock protein, Hsp 70, has been shown to play an important role in tumour immunity. Vaccination with Hsp 70-peptide complexes (Hsp70-PCs), isolated from autologous tumour cells, can induce protective immune responses. We have developed a novel method to identify synthetic mimic peptides of Hsp70-PCs and to test their ability to activate T-cells. Peptides (referred to as "recognisers") that bind to Hsp70-PCs from the human breast carcinoma cell line, MDA-MB-231, were identified by bio-panning a random peptide M13 phage display library. Synthetic recogniser peptides were subsequently used as bait in a reverse bio-panning experiment to identify potential Hsp70-Pc mimic peptides. The ability of the recogniser and mimic peptides to prime human lymphocyte responses against tumour cell antigens was tested by simulating lymphocytes with autologous peptide-loaded monocyte-derived dentritic cells (DCs). Priming and subsequent stimulation with either the recogniser or mimic peptide resulted in interferon-y (IFN-y) secretion by the lymphocytes. Further more, DCs loaded with Hsp70-PC or the recogniser or the mimic peptide primed the lymphocytes to respond to soluble extracts from breast cells. These results highlight the potential application of synthetic peptide-mimics of Hsp70-PCs, as modulators of the immune response against tumours.
Keyword(s): Biology; Peptide; mimotopes; Protein; Antigens
Publication Date:
Type: Journal article
Peer-Reviewed: Yes
Institution: Maynooth University
Citation(s): Doherty, Derek and Arnaiz, Blanca and Madrigal-Estebas, Laura and Todryk, Stephen and James, Tharappel C and Bond, Ursula (2006) A novel method to identify and characterise peptide mimotopes of heat shock protein 70-associated antigens. Journal of Immune Based Therapies and Vaccines, 4 (2). pp. 1-12.
Publisher(s): Biomed Central
File Format(s): application/pdf
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First Indexed: 2014-09-20 05:09:01 Last Updated: 2014-09-20 05:09:01