Of MHC class I molecule

Class I. These molecules are expressed on the surfaces of all nucleated cells and are recognized by CD8+ cells, also known as cytotoxic T cells. There are three subclasses of MHC class I molecules called HLA-A, HLA-B, and HLA-C. 

Park, B., Lee, S., Kim, E., and Ahn, K. (2003) A single polymorphic residue within the peptide-binding cleft of MHC class I molecules determines spectrum of tapasin dependence. /. Immunol. 170, 961. 

Defects in MHC Class II molecules, while exposing affected subjects to a variety of infections, do not result in the severe immunodeficiency seen in patients with SCID. In contrast to mutations affecting MHC Class II molecules, defects in MHC Class I molecules are rare. Mutations affecting MHC Class I molecules are directed to genes on chromosome 6 at the MHC locus that code for peptide-transporter proteins (122). The function of these transporter proteins is to transport the peptide antigens so that a complex with the a chain of MHC Class I molecules and p 2-microglobulin is formed and transported to the surface of the cell. 

The killing ability of NK cells is associated with the expression of MHC class I molecules. According to the missing-self hypothesis, NK cells search for the presence of MHC class I molecules that are ubiquitously expressed. A decrease in the expression of MHC class I molecules on a cell allows NK cells to kill the target as it is released from the influence of MHC class I molecules. The ability... 

The principal biological actions of type I IFNs include inhibition of viral replication, inhibition of cell proliferation, increase in the lytic potential of NK cells and the modulation of MHC molecule expression. They increase the expression of MHC class I molecules and decrease the expression of MHC class II molecules. 

Morrice, N. A., and Powis, S. J. (1998). A role for the thiol-dependent reductase ERp57 in the assembly of MHC class I molecules. Curr. Biol. 4, 713-716. 

Anthracyclines glycosylated at the 4-position are very rarely mentioned in the literature, and 4-0-(/l-D-glucopyranosyl)-fi-rhodomycinone (39a) isolated from a mutant of Actinomadura roseoviolacea was the first one of this series. It exhibited no antibacterial or cytotoxic activity [66]. However, its glucuronic acid derivative histomodulin (39b), isolated from Streptomyces ruber JCM3131, was reported as an up-regulator of MHC class-I molecules in B16/BL6 cells [67]. 

MHC class I, the target of gp40, is retained because of properties in its luminal domain. A deletion mutant of murine H-2K which comprises the luminal domain of the heavy chain can be detected in the supernatant of transfectants and is retained in the ER in the presence of gp40 (Figs. 5, 6A). Thus the luminal part of MHC class I molecules is sufficient for recognition by gp40. 

Ziegler H, Muranyi W, Burgert HG, Kremmer E, Koszinowski UH (2000) The luminal part of the murine cytomegalovirus glycoprotein gp40 catalyzes the retention of MHC class I molecules. EMBO J 19 870-881... 

Finally, herpesviruses produce proteins that target MHC class I heavy chains for destruction. MCMV induces degradation of MHC class I molecules in a lysosomal compartment (Reusch et al. 1999). In HCMV-infected cells, MHC class I heavy chains are targeted for destruction to the proteasome via a novel degradation pathway that will be discussed below. 

Apart from a difference in specificity toward subtypes of MHC class I molecules, US2 and USl 1 seem to react dilfcrently with MHC class I heavy chains. In cells expressing US2 or USll newly synthesized MHC class I heavy chains are rapidly degraded, regardless of whether they are correctly folded and assembled in a complex with p2m or occur as free heavy chains (Wiertz et al. 1996a,b). In pulse-chase experiments, US2 coprecipitates with heavy chain-p2m complexes and with free heavy chains, whereas for USl 1 very little or no coprecipitation with class 1... 

Ubiquitinated MHC class I molecules could be detected upon expression of USI 1, whereas in the absence of USI 1 these were undetectable (Shamu et al. 1999). Our recent study showed that a functional ubiquitin system is required for the USll mediated breakdown of MHC class I molecules in a very early stage of the degradation pathway disruption of the ubiquitin machinery in a mutant cell line causes retention of MHC class I molecules, bound to USI 1, in the ER membrane (Kikkert et al. 2001). Dislocation of the MHC class I molecules across the ER membrane is apparently fully dependent on a functional ubiquitin system. Results from a recently published in vitro study using ubiquitin depleted cytosol are in complete agreement with this (Shamu et al. 2001). 

Kikkert M, Hassink G, Barel M, Hirsch C, van der Wal FJ, Wiertz E (2001) Ubiquitination is essential for human cytomegalovirus US 11-mediated dislocation of MHC class I molecules from the endoplasmic reticulum to the cytosol. Biochem J 358 369-377... 

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