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Bioinformatics Advance Access published online on July 1, 2009
Bioinformatics, doi:10.1093/bioinformatics/btp404
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© The Author (2009). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

High throughput minor histocompatibility antigen prediction

David S. DeLuca 1,2, Britta Eiz-Vesper 1, Nektarios Ladas 1, Barbara Anna-Maria Khattab 1 and Rainer Blasczyk 1,*

1 Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany
2 Cancer Vaccine Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA

*To whom correspondence should be addressed. Rainer Blasczyk, E-mail: Blasczyk.Rainer{at}mh-hannover.de


  Abstract

Motivation: Minor histocompatibility antigens (mHags) are a diverse collection of MHC-bound peptides that have immunological implications in the context of allogeneic transplantation because of their differential presence in donor and host, and thus play a critical role in the induction of the detrimental graft-versus-host disease (GvHD) or in the development of the beneficial graft-versus-leukemia (GvL) effect. Therefore, the search for mHags has implications not only for preventing GvHD, but also for therapeutic applications involving leukemia-specific T cells. We have created a web-based system, named PeptideCheck, which aims to augment the experimental discovery of mHags using bioinformatic means. Analyzing peptide elution data to search for mHags and predicting mHags from poly-morphism and protein databases are core features.

Results: Comparison with known mHag data reveals that some but not all of the previously known mHags can be reproduced. By applying a system of filtering and ranking, we were able to produce an ordered list of potential mHag candidates in which HA-1, HA-3, and HA-8 occur in the best 0.25 per cent. By combining SNP, protein, tissue expression, and genotypic frequency data, together with antigen presentation prediction algorithms, we propose a list of the best peptide candidates which could potentially induce the graft versus leukemia effect without causing graft versus host disease.

Availability: http://www.peptidecheck.org

Contact: Blasczyk.Rainer{at}mh-hannover.de

Associate Editor: Dr. Jonathan Wren

Received on April 16, 2009; revised on June 9, 2009; accepted on June 27, 2009

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