MHC class

Fremont, D.H., Hendrickson, W.A., Marrack, P, Kappler, J. 5tructures of an MHC class II molecule with covalently bound single peptides. Science 272 1001-1004,... 

Fremont, D.H., Matsumura, M., 5tura, E.A., Peterson, P.A., Wilson, I.A. Crystal structures of two viral peptides in complex with murine MHC class I H2-K . Science 257 919-927, 1992. 

Another application was investigated by Olson and coworkers (99HCA(82) 2432). 4-Substituted-A-alkyl- and A-aryl-l,2,5-thiadiazolidin-3-ones 247-249 were prepared and evaluated for their MHC class-II inhibitor activity. 

The antiinflammatory effects of statins likely result from their ability to inhibit the formation of mevalonic acid. Downstream products of this molecule include not only the end product, cholesterol, but also several isoprenoid intermediates that covalently modify ( pre-nylate ) certain key intracellular signaling molecules. Statin treatment reduces leukocyte adhesion, accumulation of macrophages, MMPs, tissue factor, and other proinflammatory mediators. By acting on the MHC class II transactivator (CIITA), statins also interfere with antigen presentation and subsequent T-cell activation. Statin treatment can also limit platelet activation in some assays as well. All these results support the concept that in addition to their favorable effect on the lipid profile, statins can also exert an array of antiinflammatory and immunomodulatory actions. 

This class of lymphocytes differentiates from immuno-logically incompetent hematopoietic stem cells of the bone marrow within the thymus - hence, the name thymus-dependent (T-) lymphocytes. Two major subclasses develop simultaneously, T-helper lymphocytes (Th) and cytotoxic effector lymphocytes (Tc). The cytotoxic T-lymphocytes (carrying on the surface the differentiation marker CD8) destroy cells, which cany their cognate antigen bound to MHC class I molecules on the surface by inducing apoptosis. From an evolutionary point of view Tc cells appear to have developed predominantly to cope with vims infections. As vituses can only replicate within cells, Tc eliminate them by destroying their producers. 

IFN- 3 reduces the induction by inflammatory cytokines of adhesion molecules and of MHC class I and II complex on endothelial cells, a process preceding attachment and transendothelial migration of T-cells. These anti-inflammatory effects of IFN- 3 exemplify antagonistic actions of type I and type IIIFN. There is, indeed, much clinical evidence for the involvement of IFN-y in inflammatory processes - through activation of iNOS and subsequent secretion of NO - leading to the establishment of autoimmune diseases as for instance in rheumatoid arthritis. 

Group of transmembrane proteins engaged in the presentation of small peptide fragments to T-cells. Two classes of Major histocompatibility complex (MHC) molecules exist both of which are encoded by a highly polymorphic gene cluster. MHC class I and class II proteins present peptide fragments to CD8+ and CD4+ T-cells, respectively. The human MHC is also known as HLA, the murine MHC as H-2 complex. 

Bacterial or viral proteins linking T-cell receptors and MHC molecules through simultaneous interaction with the constant domains of all MHC class II molecules and of T-cell receptor (3-chains. Hence, superantigens are polyclonal T-cell activators most likely involved in the development of autoimmune diseases. 

The activation of DRF-3 through the TREF dependent pathway allows for chemokines such as RANTES to be produced. It also leads to the production of DFN-a and EFN-(3, which are involved in anti-viral immunity. The TREF pathway, activated by either TLR-3 or TLR-4, can also induce MHC class-II expression and costimulatory molecules, thus leading to T-cell activation. This provides an important link between innate and adaptive immunity. 

The Liskamp group also examined the ability of peptoid-peptide hybrids to be bound by the MHC Class II receptor, an important component of the human immune system [39]. Two of three peptoid substitutions in the 14-residue peptide caused substantial decreases in binding affinity, despite the fact that these were solvent-exposed residues. These results were attributed to a loss of hydrogen-bond contacts as well as to steric clashes caused by unfavorable positioning of the new side chain groups. 

A Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells. Nature 1997 388 782-787. 

Imai Y, Fujimori Y, Nakanishi K Basophils contribute to TH2-IgE responses in vivo via IL-4 production and presentation of peptide-MHC class II complexes to CD4+ T cells. Nat Immunol 2009 42 10 706-712. 

Perrigoue JG, Saenz SA, Siracusa MC, Allenspach EJ, Taylor BC, Giacomin PR, Nair MG, Du Y, Zaph C, van Rooijen N, Comeau MR, Pearce EJ, Laufer TM, Artis D MHC class Il-dependent basophil-CD4+ T-cell interactions promote Th2 cytokine-dependent immunity. Nat Immunol 2009 10 697-705. 

NF-xB activates genes encoding MHC class I antigens, IL-1, TNFa, IL-6, the interleukin-2 (IL-2) receptor, some acute-phase proteins and the adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) (lademarco... 

CBP Cromolyn-binding protein CCK Cholecystokinin CCR Creatinine clearance rate CD Cluster of differentiation (a system of nomenclature for sur ce molecules on cells of the immune system) cluster determinant CDl Cluster of differentiation 1 also known as MHC class I-like surfitce glycoprotein... 

CDla Isoform a also known as non-classical MHC class I-like surface antigen present on thymocytes and dendritic cells... 

CD lb Known to be present on thymocytes and dendritic cells CDlc Isoform c also known as non-classical MHC class I-like surface antigen present on thymocytes CD2 Defines T cells involved in antigen non-specific cell activation CD3 Also known as T cell receptor-associated surface glycoprotein on T cells CD4 Defines MHC class Il-restricted T cell subsets... 

CDS Defines MHC class I-restricted T cell subset present on NK cells CDIO Known to be common acute leukaemia antigen CDlla Known to be zn a chain of LFA-1 (leucocyte function antigen-1) present on several types of leucocyte and which mediates adhesion CDllc Known to be z complement receptor 4 a chain. 

An unknown antigen presented by the major histocompatibility complex (MHC) class II molecules causes T cells to become autoreactive (Fig. 26-1). Once activated, T cells penetrate the... 

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