Application of the pMHC array to characterise tumour antigen specific T cell populations in leukaemia patients at disease diagnosis


Brooks, Suzanne E., Bonney, Stephanie A., Lee, Cindy, Publicover, Amy, Khan, Ghazala, Smits, Evelien L., Sigurdardottir, Dagmar, Arno, Matthew, Li, Demin, Mills, Ken I, Pulford, Karen, Banham, Alison H, van Tendeloo, Viggo, Mufti, Ghulam J, Rammensee, Hans-Georg, Elliott, Tim J., Orchard, Kim H. and Guinn, Barbara-ann (2015) Application of the pMHC array to characterise tumour antigen specific T cell populations in leukaemia patients at disease diagnosis PLoS ONE, 10, (10), pp. 1-19. (doi:10.1371/journal.pone.0140483). (PMID:18308940).

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Description/Abstract

Immunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC) tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8+ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV) and influenza (Flu)) and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1), MelanA, Wilms' Tumour (WT1) and tyrosinase). We show that the pMHC array is at least as sensitive as flow cytometry and has the potential to rapidly identify more than 40 specific T-cell populations in a small sample of T-cells (0.8-1.4 x 10(6)). Fourteen of the twenty-six acute myeloid leukaemia (AML) patients analysed had T cells that recognised tumour antigen epitopes, and eight of these recognised PASD1 epitopes. Other tumour epitopes recognised were MelanA (n = 3), tyrosinase (n = 3) and WT1(126-134) (n = 1). One of the seven acute lymphocytic leukaemia (ALL) patients analysed had T cells that recognised the MUC1(950-958) epitope. In the future the pMHC array may be used provide point of care T-cell analyses, predict patient response to conventional therapy and direct personalised immunotherapy for patients.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1371/journal.pone.0140483
ISSNs: 1932-6203 (print)
Organisations: Cancer Sciences
ePrint ID: 395394
Date :
Date Event
25 September 2015Accepted/In Press
22 October 2015Published
Date Deposited: 27 May 2016 14:28
Last Modified: 22 Feb 2017 05:02
Further Information:Google Scholar
URI: http://eprints.soton.ac.uk/id/eprint/395394

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