High-throughput minor histocompatibility antigen prediction.
BACKGROUND
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 polymorphism and protein databases are the 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%. By combining single nucleotide polymorphism, 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 GvL effect without causing GvFD.


BACKGROUND
http://www.peptidecheck.org.
DeLuca
David S
DS
Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
Eiz-Vesper
Britta
B
Ladas
Nektarios
N
Khattab
Barbara Anna-Maria
BA
Blasczyk
Rainer
R
D000465:Algorithms; D030562:Databases, Protein; D015778:Minor Histocompatibility Antigens / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D015778:Minor Histocompatibility Antigens