Method for prediction of an immune response against mismatched human leukocyte antigens

Method for selecting and transplanting cells or a tissue preparation or organ for allogeneic transplantation comprising:

• obtaining and HLA (human leukocyte antigen)-typing a tissue sample:
• (a) from a transplant recipient or (b) from a transplant donor,
• accessing, via one or more computers, either
• a database with HLA-typing data of cells, tissue preparations or organs from multiple potential donors, or
• a database with HLA-typing data of cells, tissue preparations or organs from multiple potential recipients;
• and
• generating, via computer(s), a listing of mismatched HLA proteins-between the multiple potential donors and the transplant recipient of (a) or the one or more recipients and the transplant donor of (b), and
• determining, via the computer(s), for each of the multiple potential donors and the transplant recipient of (a) or the multiple potential recipients and the transplant donor of (b), a number of predicted indirectly recognized HLA epitopes (PIRCHES), wherein said PIRCHES are recipient- or donor- specific HLA-derived peptides from a mismatched recipient or donor -HLA protein respectively, and are predicted, by the computer(s), to be presented by an HLA molecule,
• wherein (i) the PIRCHES are identified by the computer(s) by identifying cleavage sites for the human proteasome within each mismatched HLA protein, wherein said PIRCHES are between 5 to 20 amino acids in length, and
• wherein (ii) the predicted presentation of PIRCHES identified in (i) by the HLA molecule is determined by the computer(s) by determining the IC50 binding value for binding between said PIRCHES identified in (i) and the HLA molecule, wherein PIRCHES are predicted to bind the HLA molecule when an IC50 score of ≤10 μM is determined,
• wherein the likelihood of an immune response after transplantation, wherein the immune response includes at least T-cell-alloreactivity against (HLA), is increased with an increased number of PIRCHES,
• selecting the cell or tissue preparation or organ for the allogenic transplantation from a donor from the multiple potential donors or a recipient from the multiple potential recipients with the lowest PIRCHE score of said multiple potential donors or recipients,
• and transplanting the cells, tissue preparation or organ of the donor with the lowest PIRCHE score of said multiple potential donors into the transplant recipient of (a) or transplanting the cells, tissue preparation or organ of the transplant donor of (b) into the recipient with the lowest PIRCHE score of said multiple potential recipients.