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

被引:25
作者
Felix, NJ
Brickey, WJ
Griffiths, R
Zhang, JH
Van Kaer, L
Coffman, T
Ting, JPY
机构
[1] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA
[2] Durham Vet Adm, Dept Med, Durham, NC 27705 USA
[3] Durham Vet Adm, Transplantat Lab, Durham, NC 27705 USA
[4] Duke Univ, Med Ctr, Durham, NC 27705 USA
[5] Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Howard Hughes Med Inst, Nashville, TN 37232 USA
关键词
major histocompatibility complex class II; H2-DM; class II-associated antigenic peptide; alloreactivity; transplantation;
D O I
10.1084/jem.192.1.31
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:31 / 40
页数:10
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