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Original Article

H2-DM^–/– Mice Show the Importance of Major Histocompatibility Complex–Bound Peptide in Cardiac Allograft Rejection

^a University of North Carolina Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
^b Department of Medicine and the Transplantation Laboratory, Durham Veterans Administration and Duke University Medical Center, Durham, North Carolina 27705
^c Howard Hughes Medical Institute, Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
CB# 7295, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295.919-966-3015919-966-5538

panyun{at}med.unc.edu

The role played by antigenic peptides bound to major histocompatibility complex (MHC) molecules is evaluated with H2-DM^–/– mice. These mice have predominantly class II–associated invariant chain peptide (CLIP)-, not antigenic peptide–bound, MHC class II. H2-DM^–/– donor heart grafts survived three times longer than wild-type grafts and slightly longer than I-A_β^b–^/– grafts. Proliferative T cell response was absent, and cytolytic response was reduced against the H2-DM^–/– grafts in vivo. Residual cytolytic T cell and antibody responses against intact MHC class I lead to eventual rejection. Removal of both H2-DM 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.

Key Words: major histocompatibility complex class II • H2-DM • class II–associated antigenic peptide • alloreactivity • transplantation

© 2000 The Rockefeller University Press

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