Structure and function of major histocompatibility complex class I antigens.
ABSTRACT Major histocompatibility complex (MHC) class I molecules control the repertoire and function of CD8 T cells and NK cells, and both cell types are involved in transplant rejection. Understanding the regulatory role of MHC class I molecules is important in the design of better therapies. This review article focuses on molecular aspects of alloreactive recognition of MHC class I molecules by CD8 T cells and NK cells and on the functional activities of CD8 T cells and NK cells in transplant rejection and tolerance.
Recent T cell receptor (TCR)-peptide-MHC class I crystal structures and structural and functional analyses of MHC class I interactions with NK cell inhibitory receptors have revealed new insights into molecular aspects of allorecognition of MHC class I molecules by CD8 T cells and NK cells. In functional studies, CD8 T cells and NK cells have been shown to have conditional and model-dependent roles in allograft rejection. NK cells have also been shown to have an unexpected role in tolerance induction in the transplantation setting.
Both CD8 and NK cells play diverse roles in graft rejection and tolerance induction. Further understanding of molecular interactions between MHC class I molecules and TCRs or NK receptors is important and highly relevant to transplantation.
- SourceAvailable from: Adiba IsaStem Cells in Clinic and Research, 08/2011; , ISBN: 978-953-307-797-0
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ABSTRACT: The mutated major histocompatibility complex (MHC) class I that contains donor-type epitopes displayed on recipient-type molecule was show-n to inhibit acute and chronic rejection and in-duce indefinite survival of heterotopic cardiac allografts when administered in combination with a sub-therapeutic dose of cyclosporine (CsA) in a rat transplantation model. To eluci-date the molecular pathways involved in the immunosuppressive effects of the mutated MHC molecule, we analyzed gene and protein ex-pression profile during early and late phase following post-transplantation. Cytoskeletal str-ucture analysis and expression status of Rho GTPase proteins, vacuolar transport and cy-toskeleton regulatory pathways involved in im-mune response in T and dendritic cells demon-strated the novel mechanism for the abrogation of chronic rejection. Our studies confirm a new role of Rho GTPase pathway in the modification of T cell motility and infiltration of the graft. We dis-cuss these results within the framework of the most recent literature on MHC and molecular machinery controlling T cell functions and den-dritic cell antigen presentation.