Frontiers in Immunology (Nov 2014)

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

  • Max eJameson-Lee,
  • Vishal eKoparde,
  • Phil eGriffith,
  • Allison eScalora,
  • Juliana K Sampson,
  • Haniya eKhalid,
  • Nihar U Sheth,
  • Michael eBatalo,
  • Myrna G Serrano,
  • Catherine H Roberts,
  • Michael L Hess,
  • Gregory A Buck,
  • Michael C Neale,
  • Masoud H Manjili,
  • Amir Ahmed Toor

DOI
https://doi.org/10.3389/fimmu.2014.00529
Journal volume & issue
Vol. 5

Abstract

Read online

Donor T cell mediated graft versus host effects (GVH) may result from the aggregate alloreactivity to minor histocompatibility antigens (mHA) presented by the HLA molecules in each donor-recipient pair undergoing stem cell transplantation (SCT). Whole exome sequencing has previously demonstrated a large number of nonsynonymous 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 was 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 an HLA-specific alloreactivity potential.

Keywords