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

The role played by antigenic peptides bound to major histocompatibility complex (MHC) molecules is evaluated with H2-DM alpha(-/-) mice. These mice have predominantly class II-associated invariant chain peptide (CLIP)-, not antigenic peptide-boundl MHC class II. H2-DM alpha(-/-) donor heart grabs survived three times longer than wild-type grafts and slightly longer than I-A(beta)(b-/-) grafts. Proliferative T cell response was absent, and cytolytic response was reduced against the H2-DM alpha(-/-) grafts in vivo. Residual cytolytic T cell and antibody responses against intact MHC class I lead to eventual rejection. Removal of both H2-DM alpha and beta 2-microglobulin (beta 2m) in cardiac grafts lend to Beater (8-10 times) graft survival, whereas removal of beta 2m alone did not have any effect. These results demonstrate the significance of peptide rather than just allogeneic MHC, ill eliciting graft rejection.