Cancer esearch oenvironment and Immunology h-Throughput Characterization of 10 New Minor ocompatibility Antigens by Whole Genome R ociation Scanning

nloaded ents with malignant diseases can be effectively treated with allogeneic hematopoietic stem cell transtion (allo-SCT). Polymorphic peptides presented in HLA molecules, the so-called minor histocompatantigens (MiHA), play a crucial role in antitumor immunity as targets for alloreactive donor T cells. fication of multiple MiHAs is essential to understand and manipulate the development of clinical ses after allo-SCT. In this study, CD8 T-cell clones were isolated from leukemia patients who entered ete remission after allo-SCT, and MiHA-specific T-cell clones were efficiently selected for analysis of ition of a panel of EBV-transformed B cells positive for the HLA restriction elements of the selected clones. One million single nucleotide polymorphisms (SNP) were determined in the panel cell lines and igated for matching with the T-cell recognition data by whole genome association scanning (WGAs). cant association with 12 genomic regions was found, and detailed analysis of genes located within these ic regions revealed SNP disparities encoding polymorphic peptides in 10 cases. Differential recognition ient-type, but not donor-type, peptides validated the identification of these MiHAs. Using tetramers, t populations of MiHA-specific CD8 T cells were detected, demonstrating that our WGAs strategy distinc allows high-throughput discovery of relevant targets in antitumor immunity after allo-SCT. Cancer Res; 70(22); 9073–83. ©2010 AACR.