In silico Derivation of HLA-Specific Alloreactivity Potential from Whole Exome Sequencing of Stem-Cell Transplant Donors and Recipients: Understanding the Quantitative Immunobiology of Allogeneic Transplantation

Donor T-cell mediated graft versus host (GVH) effects may result from the aggregate alloreactivity to minor histocompatibility antigens (mHA) presented by the human leukocyte antigen (HLA) molecules in each donor-recipient pair undergoing stem-cell transplantation (SCT). Whole exome sequencing has p...

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Bibliographic Details
Published in:Frontiers in immunology 2014, Vol.5, p.529-529
Main Authors: Jameson-Lee, Max, Koparde, Vishal, Griffith, Phil, Scalora, Allison F, Sampson, Juliana K, Khalid, Haniya, Sheth, Nihar U, Batalo, Michael, Serrano, Myrna G, Roberts, Catherine H, Hess, Michael L, Buck, Gregory A, Neale, Michael C, Manjili, Masoud H, Toor, Amir Ahmed
Format: Article
Language:English
Subjects:
allogeneic stem cell transplantation
alloreactivity
exome sequencing
HLA-peptide binding affinity
Immunology
Peptides
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Summary:Donor T-cell mediated graft versus host (GVH) effects may result from the aggregate alloreactivity to minor histocompatibility antigens (mHA) presented by the human leukocyte antigen (HLA) molecules in each donor-recipient pair undergoing stem-cell transplantation (SCT). Whole exome sequencing has previously demonstrated a large number of non-synonymous single nucleotide polymorphisms (SNP) present in HLA-matched recipients of SCT donors (GVH direction). The nucleotide sequence flanking each of these SNPs was obtained and the amino acid sequence determined. All the possible nonameric peptides incorporating the variant amino acid resulting from these SNPs were interrogated in silico for their likelihood to be presented by the HLA class I molecules using the Immune Epitope Database stabilized matrix method (SMM) and NetMHCpan algorithms. The SMM algorithm predicted that a median of 18,396 peptides weakly bound HLA class I molecules in individual SCT recipients, and 2,254 peptides displayed strong binding. A similar library of presented peptides was identified when the data were interrogated using the NetMHCpan algorithm. The bioinformatic algorithm presented here demonstrates that there may be a high level of mHA variation in HLA-matched individuals, constituting a HLA-specific alloreactivity potential.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2014.00529