H2-DMα-(/)- mice show the importance of major histocompatibility complex-bound peptide in cardiac allograft rejection

Abstract

The role played by antigenic peptides bound to major histocompatibility complex (MHC) molecules is evaluated with H2-DMα-(/)- mice. These mice have predominantly class II-associated invariant chain peptide (CLIP)-, not antigenic peptide-bound, MHC class II. H2DMα-(/)- donor heart grafts survived three times longer than wild-type grafts and slightly longer than I- Aβ(b-(/)-) grafts. Proliferative T cell response was absent, and cytolytic response was reduced against the H2-DMα-(/)- grafts in vivo. Residual cytolytic T cell and antibody responses against intact MHC class I lead to eventual rejection. Removal of both H2-DMα and β2-microglobulin (β2m) in cardiac grafts lead to greater (8-10 times) graft survival, whereas removal of β2m alone did not have any effect. These results demonstrate the significance of peptide rather than just allogeneic MHC, in eliciting graft rejection.