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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.; Guinn, Barbara-ann

Authors

Suzanne E. Brooks

Ken I. Mills

Karen Pulford

Alison H. Banham

Viggo van Tendeloo

Ghulam J. Mufti

Hans-Georg Rammensee

Tim J. Elliott

Kim H. Orchard

Stephanie A. Bonney

Cindy Lee

Amy Publicover

Ghazala Khan

Evelien L. Smits

Dagmar Sigurdardottir

Matthew Arno

Demin Li

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 106). 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 WT1126-134 (n = 1). One of the seven acute lymphocytic leukaemia (ALL) patients analysed had T cells that recognised the MUC1950-958 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.

Journal Article Type Article
Publication Date Oct 22, 2015
Journal PLOS ONE
Print ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 10
Issue 10
Article Number e0140483
DOI https://doi.org/10.1371/journal.pone.0140483
Publisher URL https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0140483

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Copyright Statement
Copyright: © 2015 Brooks et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited



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