Variable hematopoietic graft rejection and graft-versus-host disease in MHC-matched strains of mice

Abstract

MHC typing for human hematopoietic cell transplantation (HCT) from unrelated donors is currently performed by using a combination of serologic and molecular techniques. It has been determined that allelic differences in human MHC molecules, revealed by nucleotide sequencing but not by serologic typing, substantially influence graft rejection and graft-versus-host disease, two serious complications of clinical HCT. We studied transplantation of purified hematopoietic stem cells in a series of mouse strains that were matched at the MHC but had different background genes, and we observed striking differences in engraftment resistance and graft-versus-host disease severity, both factors depending on the donor-recipient strain combination. The individual mouse lines studied here were established nearly a century ago, and their MHC types were determined exclusively by serologic techniques. We considered the possibility that serologically silent MHC polymorphisms could account for our observations and, therefore, we performed DNA sequencing of the class I and II MHC alleles of our mouse strains. At each locus, exact homology was found between serologically MHC-matched strains. Our results likely extend to all serologically MHC-matched mouse strains used in modern research and highlight the profound and variable influence that non-MHC genetic determinants can have in dictating outcome after HCT.

View details for DOI 10.1073/pnas.2035077100

View details for Web of Science ID 000185685700072

View details for PubMedID 14504392

View details for PubMedCentralID PMC208799