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The search for minor histocompatibility antigens (mHags) has implications not only for
preventing graft versus host disease, but also for therapeutic applications involving
leukaemia-specific T cells. In the context of hematopoietc stem cell transplantation,
any polymorphic gene can potentially be an mHag-source, with the additional
requirement that the polymorphism leads to a differential T cell epitope expression.
We have filtered over 18,000 entries which represent protein variations in NCBI’s
dbSNP polymorphism database describing 15,000 genes which could potentially encode
minor antigens. Almost a thousand of these genes contain null allele variants,
having important implications because the whole protein sequence is allogeneic
(whereas a single nucleotide polymorphism results in a single amino acid
difference). Additionally, our group has produced an expression profile of graft
versus leukaemia-specific genes using affymetrix DNA chips. Of the resulting 500
GvL-specific genes, 235 were found to be polymorphic. Of the 28,000 theoretically
possible nonamers, 131 were predicted to be both processed by the
immunoproteasome as well as presented by clinically relevant HLA alleles.
These peptides, encoded by 40 genes, represent the most likely candidates to
produce a leukaemia-specific alloreactive T cell response. The fully automated
nature of this system is necessary to regenerate results in response to an
ever-increasing pool of biological data.
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Title
PeptideCheck - mHag, SNP, HLA peptide binding prediction search for (GvL) immunotherapy
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Description
PeptideCheck searches for minor histocompatibility antigens for developing alloreactive
lymphocytes using SNP data and HLA peptide binding/epitope prediction for Graft vs
leukemia (GvL) immunotherapy
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Keywords
Snp,gvhd,gvl,graft versus host disease,graft versus leukemia,epitope,hla,mhc,binding,peptide,prediction,search,mhag,minor histocompatibility antigen,t-cell,peptidecheck,immunotherapy,bmt,bone marrow
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