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

Felix NJ, Brickey WJ, Griffiths R, Zhang J, Van Kaer L, Coffman T, Ting JP
J Exp Med. 2000 192 (1): 31-40

PMID: 10880524 · PMCID: PMC1887714 · DOI:10.1084/jem.192.1.31

The role played by antigenic peptides bound to major histocompatibility complex (MHC) molecules is evaluated with H2-DMalpha(-/)- mice. These mice have predominantly class II-associated invariant chain peptide (CLIP)-, not antigenic peptide-bound, MHC class II. H2-DMalpha(-/)- donor heart grafts 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-DMalpha(-/)- grafts in vivo. Residual cytolytic T cell and antibody responses against intact MHC class I lead to eventual rejection. Removal of both H2-DMalpha and beta2-microglobulin (beta2m) in cardiac grafts lead to greater (8-10 times) graft survival, whereas removal of beta2m alone did not have any effect. These results demonstrate the significance of peptide rather than just allogeneic MHC, in eliciting graft rejection.

MeSH Terms (18)

Animals Antigens, Differentiation, B-Lymphocyte Cytokines Graft Rejection Heart Transplantation Histocompatibility Antigens Class I Histocompatibility Antigens Class II HLA-D Antigens Major Histocompatibility Complex Mice Mice, Inbred BALB C Mice, Inbred DBA Mice, Inbred Strains Mice, Knockout Myocardium Th1 Cells Th2 Cells Transplantation, Homologous

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